xt7mkk94bv29 https://exploreuk.uky.edu/dips/xt7mkk94bv29/data/mets.xml University of Kentucky. Office of the Vice President for Research and Graduate Studies Kentucky University of Kentucky. Office of the Vice President for Research and Graduate Studies 2003 volumes. Call Number: LD2762.9 .K38c. Accession Number: 2018ua049 journals LD2762.9 .K38c English Office of the Vice President for Research and Graduate Studies  Contact the Special Collections Research Center for information regarding rights and use of this collection University of Kentucky Odyssey Magazine Research -- Kentucky -- Periodicals Education -- Research -- Periodicals Research -- Kentucky Odyssey: The Magazine of University of Kentucky Research and Graduate Studies, Spring 2003 text images Odyssey: The Magazine of University of Kentucky Research and Graduate Studies, Spring 2003 2003 2003 2026 true xt7mkk94bv29 section xt7mkk94bv29 UK UNIVERSITY OF KENTUCKY

 

  

lee Ti Todd lri, President

Wendy Baldwin, Vice President for Research

Delwood C, Collins, Associate Vice President for Research
loseph L. Fink lll, Associate Vice President for Research

Agriculture
\l. Mott Smith, Dean

Arts and Sciences
Houard Crotch, Dean

Business and Economics
Richard \\ Furst, Dean

Eggnfsyogfligfsmdies University of Kentucky Research
J Dmidluhnson, Dean S p r i n Q 2 0 O 3
Dentistry

lc-(in A \ssatl, Dean

Design
David \lolint‘i, Dean

Education
James (lbulka, Dean

Engineering
Thomas ll tester, Dean

Fine Arts
Robert Shai, Dean

Health Sciences
Thoma“ Robinson, Dig-an

Human Environmental Sciences
\l, Scott Smith, Acting Dean

Cover Story

Clinical Trials: A Human Safety Net

for New Drugs and Treatments

UK researchers are fighting disease on new fronts
through clinical trials focused on more effective
treatment for lung cancer, macular degeneration,
diabetes, hormone replacement therapy, asthma,
and thyroid cancer. 4

law
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Medicine

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Nursing

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Pharmacy
kcnnclh B Rooerts, Dean

Social Work
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Odyssey

Director
Deborah Hers

“1"“ Features

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Associate Editor and Web Designer From the Beltway t0 the Bluegrass
Alicia P Oregon
Designer Armed With 30 years experience at the NIH. Wendy Baldwin
Shear & smut is happy to be back in Kentucky and working to strengthen
Photogmpher 7 UK’s research programs. 2
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cnl: rpnsv 7 . Putting Away the Past
Z3535?:dfsij'yiiflgfizltj‘if)? " ' ‘ Kate Chard designed a highly successful therapy program
Li Ream cumumrm ' 9 —11 years in the making—to help adults process and
333 Billie” ”a“ , , overcome childhood sexual abuse. 22
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Under Pressure

UK scientists are creating tomorrow’s nanoscale
ceramic materials with pressurized CO, and
fluorinated surfactants. 26

Beware the Shape-shifter

Glenn Telling is trying to answer the question
of whether deer and elk killer CWD, following
mad cow‘s precedent, could spawn a disease
that infects humans. 34

2002-2003 University Research Professors

Thomas Leinbach: Bolstering Indonesia’s
Rural Economy

Gary Ferland: Configuring Quasars
Andrew Klapper: Finding Structure in Randomness
Timothy McClintock: Making Sense of Smell 40

Research Outreach
Prime Number: 22 Million (Dollars)

One of the largest grants ever received by UK will
support math and science teaching in 52 Appalachian
school districts. 30

BookEnd

Hollywood’s lndian

UK‘s Armando Prats follows a childhood love
of the Western to publish a book on myth and
identity in the American Western. 44

L‘flr/rfc/j /
l,

 

 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   

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3

From the Beltway
o the Bluegrass

he University of Kentucky’s new vice president for research feels like she‘s come home.

“Yes. even though it’s been 30 years since I left UK as a freshly minted Ph.D.. I do feel like
Eam ‘coming home.‘" says Wendy Baldwin, who took over UK‘s more than $20ilmillion-a—year
research enterprise the first of this year. After receiving a BA. in sociology in 1967 from Stetson
University in Deland. Florida, she worked in New York City as a social worker. But then a
simple phone call changed her life.

“A good friend of mine working on a PhD. in sociology called me from Lexington. ‘You
ought to come here.‘ she said. ‘They have a great sociology program.‘ So I decided to come
to UK sight unseen. lsqueezed all my possessions—and my two cats—into my Austin Healey
300i). and headed for the Bluegrass." says Baldwin, who had never been to Kentucky.

A Pennsylvania native, she earned two advanced sociology degrees from UK: a master‘s in
1970 and a PhD. in 1973.

Baldwin. whose affable and engaging nature strikes you immediately, brings to UK 30
years of experience at the National Institutes of Health (NIH) in Bethesda, Maryland. one
of the nation’s largest federal funding agencies, where for the past nine years she served
as deputy director for extramural research. She says extramural research is the largest part

HK/flfl

rm

  

of NIH, accounting for over 80 percent
of the $27 billion annual budget. Each
year the agency supplies funding to
more than 50,000 investigators affili—
ated with 1,700 universities, small busi-
nesses, academic medical centers, and
other research facilities worldwide
through a process of competitive peer
review.

Baldwin says there were two primary
reasons she wanted to come to UK. “I
think the university is poised to grow
academically, and the administration is
totally committed to strengthening UK.
There is such energy here to build the
research program, and itseemed like my
background was a good fit with UK’s
goals.”

Baldwin was also impressed with
Kentucky‘s commitment to higher edu—
cation that resulted in the Research Chal-
lenge Trust Fund (RCTF), more
commonly known as Bucks for Brains,
which was established in 1997. (For
more information on RCTF, go to
www.rgs.uky.edu/ca/rctf.) “For some
time now, I‘ve been holding up Ken—
tucky as an example of how the state/
university working relationship can be
mutually beneficial,“ she says.

But Baldwin realizes she has arrived at
UK at a challengingtime. “Moststates are
facing hard choices in their budgets——
Kentucky is not alone,” she says. “De
spite this, we need to repeat our message
over and over: when the state supports
the mission of a research university—a
crucial partnership—there are not only
significant economic returns and intel-
lectual returns, but also advances in
the quality of life for our citizens."

Buildingvarious types ofpartnerships
has been Baldwin's stock-in—trade at
NIH. “I went there on a two-year ap—
pointment and, well, those two years

    

turned into 30.” She says she particu-
larly enjoyed working on extramural
funding with universities like UK. “NIH
can’t fund research unless there are
universities out there that can do the
work. Most of my career has been spent
working with the academic commu—
nityto helpthem developtheirresearch
programs and also make successful
applications to NIH.”

In her work at NIH, Baldwin has seen
firsthand how extremely competitive
research funding is, and she believes
research universities can’t rest on their
laurels when it comes to funding suc—
cesses. She says one way research uni-
versities can stay competitive is to
continually look at how they are sup—
porting their researchers, especially
new faculty. “It’s hard to get started in
research, and it‘s important that young
talent be nurtured That has implica—
tions for how postdocs are treated, how
an office like mine is able to demystify
the process of seeking external fund-
ing,andhowseed moneyis madeavail-
able,” says Baldwin.

Another challenge, she says, is the
need to link up researchers who have
common interests. “Universities and
the federal funders are all struggling
with how to identify those areas that
truly need an interdisciplinary ap-
proach and then how to ensure that
people can work together effectively.
That goes to the heart of how an institu—
tion is organized: Does the system re-
ward faculty who work together across

    

department or college lines?"

Baldwin, whose enthusiasm and en—
ergy are contagious, is looking forward
to these challenges at UK while focus—
ing on her primary goal of helping to
build research programs. “One of the
things I’m proudest of at NIH was help-
ing to create a bioengineering consor—
tium. The problem had been that
bioengineering was spread all across
the 24 NIH institutes and centers. We
were able to bring all of that together
and launch a new program that has put
about $150 million into this area for the
NIH," Baldwin explains.

Breakthroughs in bioengineering re—
search, she says, can directly affect our
health and well—being. In the biomedi-
cal arena, for example, the genome
project has taken giant steps in map-
ping the genome; now the challenge is
to understand how those genes func—
tion and the role of proteins. These
advances will eventually help us better
understand diseases and enable us to
successfully target therapies.

Baldwin has also worked on a broad
array of policy issues such as human
subjects protections, reduction of regu—
latory burdens and conflicts of inter-
est. “These are all issues that are critical
for universities to address and that call
for a strong partnership with the fed-
eral government," she says.

“Right now, I’m doing a lot of listen—
ing," Baldwin says. “I'm interested in
what our faculty think about current
research programs and about launch—
ing new programs. I also want to work
with faculty and staff to further
strengthen our outreach efforts. As
Kentucky'sflagshipuniversity,we have
a bottom—line responsibility to do what
we can to improve the lives of
Kentuckians.”

  

linical trials have suffered their share of tribula-
tions lately.

The April 22, 2002. issue of Time included a lengthy article
titled “At Your Own Risk" that chronicled the slipshod study
headed up by Dr. Michael McGee at the St. John Medical
Center in Tulsa, Oklahoma. His experimental vaccine for
malignant melanoma, a particularly nasty type of cancer, was
making over a third of the trials participants sick, a fact that
McGee kept to himself before the trial was shut down.

¥ar more serious was the outcome of a clinical trial in
Maryland. Ellen Roche. 24. a technician at the Johns Hopkins
Asthma and Allergy Center, was one of three healthy volun-
teers who agreed to participate in a Hopkins clinical asthma
trial to evaluate the effects of a chemical irritant. Two days
after inhaling the chemical, Roche developed a cough, fever
and muscle pain. These ailments soon led to respiratory
distress. and within a month she was dead.

  

. ‘4 s. . v,
A Human Safety Net

These incidents—end others that have been spotlighted in
the press—have led some people to overgeneralize the dan—
gers of clinical trials.

“Although there are some risks associated with most clinical
trials, the truth is that clinical trials are usually very safe—the
vast majority of subjects are not harmed,” says Ada Sue
Selwitz, director of the Office of Research Integrity (ORl) at the
University of Kentucky. The OR] supports six federally mari—
dated review committees: three Medical and a Nonmedical
institutional Review Board (IRB), the Institutional Animal
Care and Use Committee, and the Radioactive Drug Research
Committee.

“Clinical trials are a vital and necessary part of America‘s
medical research system. They have proven to be the best
mechanism for testing potential drugs and separating the
ones that work from the onesthat are ineffective or potentially
harmful‘" says Selwitz, who is past president of the Applied

  

for New Drugs and Treatments

 Research Ethics National Association and currently a mem-
ber of the NIH Regulatory Burden Working Group. “Almost all
medical and bioethical experts agree that it‘s important to
have clinical trials and that it‘s equally essential to put into
place protective safeguards for patients."

Assuring that these safeguards are in place is at the heart of
lRBs. At UK, the [RB—a group of doctors. other health—care
providers, and community meinbers—reviews all research
studies to protect the rights of research volunteers and ensure
that the study doesnt cause unnecessary risk to participants.
Selwitz says that even before it was required by federal regu—
lations in 1981, UK established an institutional review board
because the university “has always been committed to con—
ducting ethically appropriate research

Across campus in his VA Hospital office. John Thompson.
who has been a professor of medicine at UK since 1980, helps
researchers with the nuts and bolts of clinical trials. Thomp-
son now heads up the University of Kentucky Clinical Re—
search Organization (UKCRO). which does everything from
helping to train researchers on how to conduct clinical trials
to providing the critical link between faculty and industry.
[For more information on UKCRO. go to www.mcukyedu/
ukcro.]

“The bottom line is, there is a web of protection that governs
clinical research." says Wendy Baldwin. UK's new vice presi—
dent for research. “The lRB is a vital part of this web, but we
shouldn't lose sightofthe importanceofeducating allourstaff
who are conducting clinical studies. Trained staff are really
the front line in protecting people who participate in clinical
trials. Other safeguards include data safety monitoring boards
that are specifically constituted to assess ongoing risks and
benefits of a trial and federal agencies such as NIH and the
FDA, which provide additional oversight," says Baldwin. who
brings 30 years' experience at NIH to her position at UK [see
article on page 2].

There are currently 531 clinical trials under way at UK.
according to Larry lten. associate director of the 0R1. Over
1,400 researchers are involved in these trials, and many work
on more than one. For more information on how to participate
and the research expertise available at UK, go to
www.mc.ukyedu/research/clinicaltrialshtm. Meanwhile,
read about six of these research trials in the pages that follow.

unQ cancer

The headlines blared WE'RE /
NUMBER 1! The news being
trumpeted wasn't in the/
sports section. This wasn‘t
about Kentucky basket— '
ball. it was about the lat— 5 «,
est lung—cancer rates in iii
the United States. and the l I
bad—but not surprising— '
news was that Kentucky‘s
1999 lung cancer numbers led the nation among men and
women.

“Kentucky stands out not only as the number one state. but
it‘s been thatway foralongtime." saysTimothy l\lullett,alung
surgeon and director of the University of Kentucky's
Multidisciplinary Lung Cancer Program. This year it‘s esti-
mated that 3.l()0 Kentuckians will die of lung cancer. “There's
about 50 percent more lung cancer in Kentucky than the
national average," says Alfred Cohen. director of UK‘s Markey
Cancer Center. "That’s catastrophic."

The disease kills 75 to 80 percent of those it infects, Accord-
ing to the American Cancer Society, this year more people will
die from lung cancerthan from breast. prostate and colorectal
cancers combined.

Two UK researchers are working to reverse these stats with

     

 

     

  
    
 
 
 
 
 
 
  

John Yannellt (foreground) and Edward Hirsc howitz ha\ e t reated a novel \aci ine to redu< e the

riskof lung cancer recurrence. kentucky’s 1999 lung cancer rates were the highest in the nation

among men and women.

a novel vaccine they created to reduce the risk of lung cancer
recurrence. John Yannelli, an associate professor of medi-
cine, and Edward Hirschowitz. an assistant professor of medi—
cine, are heading up a two-year clinical trial that will involve
up to 30 patients diagnosed with non-small lung cancer who
have already undergone surgery, radiation or chemotherapy.
Non—small lung cancer is moderately fast-growing and best
treated by surgical resection, and according to Hirschowitz.
accounts for 75 percent of all diagnosed lung cancers. The
trial is being funded by the Kentucky Lung Cancer Tobacco
Settlement Fund and the CancerTreatment Research Founda-
tion. a national philanthropic agency based in Chicago.

“Although the vaccine will not prevent lung cancer in those
who have never had it. we’re hoping that it can prevent the
disease from returning and help maintain remission periods
after treatment,” Hirschowitz says, as reported in the Lexing—
ton Herald-Leaderlast June. adding that even afterlung cancer
surgery that is deemed “successful." patients have a 15 to 50
percent chance of recurrence. “Because additional medical
therapies are not generally recommended until recurrences
are seen, we are using the window between medical and
surgical therapy and recurrence to enhance the body’s im—
mune response to residual cancer."

Hirschowitz and Yannelli,with the aid ofwhatYannellicalls
a “very talented and indispensable" support staff. make this
vaccine in an eight—step process. First. through a procedure
called leukapheresis, the patient’s dendritic cells—the most
potent immune—inducing cells in the body—are taken. Tech—
nicians duplicate them in the lab and mix them with cancer

proteins derived from lung cancer
cells. Oncethedendritic cellsingest
the lung cancer proteins. they are
retrained to direct the immune sys-
tem to target and kill cancer cells.

“This process takes seven days."
Yannelli explains. "We‘ve grown the
number of cells up to verv large
numbers: at seven days we harvest a
hundred million dendritic cells." The
researchers put the cells. which are
now in full combat gear. in an iniect~
able saline solution. the vaccine.

“The beauty of this vaccine." Yannelli says. "is that it stimu-
lates cells to attack only tumor cells. it does not attack llt )rmal
tissue as past treatments have. These cells that we create are
very. very smart."

Each patient receives two three—milliliter injections of the
dendritic cells. one month apart. The researchers think that
when the cells are delivered to the patient. they will travel to
the lymph nodes and stimulate the immune system to seek
and destroy cancer cells. “We dont know everything about
the immune system. but we‘re taking advantage ( if what we do
understand. letting the biology take care of business in react—
ingto an infection orother foreign proteins.“ l lirschowitz says.

There have been no major side effects from the injection so
far in the trial, Yannelli says. only local reactions such as a
small welt similar to what any of us might see after an allergy
shot.

“We‘re doing something during a time when nothing else is
offered.” Hirschowitz says. “You can either sit on the couch
waiting for your cancer to grow. or you can try something.”

“Lung cancer is particularly aggressive.” adds Yannelli. ”We
expect a recurrence—if there is one»—to happen within three
years. if someone doesn’t have a recurrence in five years.
they’re cured. My fondest hope is to see my patients hack in
the clinic in five years and say—as they leave the room—‘See
you at the UK game.”

Forlnformalion on how to parlicipa/e in [his clinical trial, call
the Pulmonary Research Office (11‘ 859/25 7—95 75,

  
     

Odyssey
visit us online

www.rgs.uky.edu

UK

UNIVERSITY OF KENTUCKY

    

    

Odyssey

   
       
 

visit us online

www.rgs.uky.edu

UK

UNIVERSITY OF KENTUCKY

  

acular Degeneration

“The eye is an extremely unforgiving
organ.“ says Jayakrishna Ambati, an
associate professor of ophthalmology
at UK. "And because ofthis, our work is
all the more challenging."

The eye placesapremium on optical
clarity. he explains, and new blood
vessels that grow in the eye interfere
with clarity and are the main culprits in
driving the disease called macular de—
generation.

Why do new blood vessels grow?
“The truth is. we aren‘t sure," says
Ambati. “ltcould be because asthe eye
grows (it's about 50 percent largerwhen
were adults). various deposits form in
the back ofthe eye and promoteamild
degree of inflammation, which may
trigger the formation of new blood ves-
sels." As new blood vessels develop,
they bleed and leak fluid because
they‘re so fragile, and injure the retina.

“Unfortunately all this is happening
in the tiny. one—millimeter region in the
center of your eye. If it happened any-
where else, it wouldn‘t be much of a
problem.“

Ambati, working with UK ophthal-
mologist Andrew Pearson, is trying to
find answers to basic biological ques—
tions about diseases of the eye, specifi—
cally—in two ongoing clinical
trials—the origin and progression of
age-related macular degeneration
(AMD).

“AMD is the leading cause of blind-
ness not only among the elderly in this
and other developed nations, but be-

cause ofthe inver-
sion of the popula-
tion pyramid in this
country, it’s the leading

causeofblindnessamong
adults, period," Ambati , .5 "

explains. “It‘s now a real-

ity for the baby boomers."

In the United States in 2000

there were 35 million senior citizens
(12.4 percent of the population was
overthe age of 65), according to David
Wekstein, associate director of UK‘s
Sanders-Brown Center on Aging. This
number is expected to grow to around
40 million by 2010 and to 70 million by
2030.

“We are clearly becoming a more
geriatric population,” saysAmbati. “and
therefore diseases associated with ag-
ing are of tremendous public health
importance.”

Currently. the only approved treat—
ment for AMD is something called pho—
todynamic therapy (PDT), which
involves injection of the dye visudine.
This drug accumulates preferentially
throughout the body. but notsolely, in
areas of new blood vessels. “We use a
laser beam to activate that drug, which
then closes off blood vessels and causes
themto stopleaking,“ Ambati explains.
But this treatment, he adds, “leaves a
lot to be desired."

For one thing, only about 20 percent
of people with macular degeneration
are eligible for this treatment—those
who fall into the category of “classic

   
   
 

Once approved, a clinical trial goes
through four phases:

Phase I: Researchers give the drug to
a small number of people to see what
dose is safe.

Phase II: Researchers give a larger
number of participants the appropriate
dose over a longer period oftime to see
ifthe drug is working and whether it has
any long-term side effects.

Phase III: Researchers give the drug
to a much larger group of people over
several months or years to see whether
the drug remains useful or has any side
effects that only show up after a longer
period of time.

Phase IV: Researchers continue to
study the drug even after it has been
approved in what are called “post-mar-
keting” trials. They can then watch for
any side effects or problems that may
show up after several years of treat-
ment.

 

 g2

 

n u

leakage. Most patients have the other type, occult leakage, doctors will target the eye by implanting a device called
which doesn’t respond well at all to photodynamic therapy." Envision TD, developed in part by Pearson at the UK Chandler
Ambati is quick to add that PDT doesn’t restore vision; all Medical Center. The device is a tiny polymer shell contain-
it does is decrease the rate of vision loss. “Also, it‘s not ing about two milligrams of the drug.
a permanent effect—95 percent of these vessels re- Thetrial, which is scheduled to run until March 2006,
open within two to three months, so treatment has to _ is fully enrolled and is well under way, with 50 trial
be repeated over and over again.“ 1 participants placed at random into three groups: one
In one of their current clinical trials—a Phase II trial 1 gets a placebo, one gets an implant, and the third gets
focused on patients with occult age-related macular the implant and photodynamic therapy. (Ambati
degeneration~Ambati and Pearson are testing did the implant procedure for those who
the effectivenessofanimplantcontainingthe fell into groups two and three. While
steroid fluocinoloneacetonide.Steroids have the patients were awake and under
long been known to be potent anti—inflam- local anesthetic, he inserted the de-
matory agents, and theideainthisstudy is to vice during a 15—minute procedure,
deliver high doses to the eye and no place suturing the polymer shell in place.)
else, since steroids given systemically are Though he's clearly excited bythe
known to have severe side effects. The basic science of trying to better un—
derstand the causes of macular de-
generation, Ambati prefers to talk
about how such work can help
people.
“Around 25 percent of people over
65 have some form of macular degen—
eration—that‘s a huge number," he says.
“Next to life itself, vision is the most
precious thing we have. When people get
older and enter their retirement years. they
have more time to read and to watch televi-
sion, and obviously they want to continue to
be able to see the faces of their grandchildren.
Macular degeneration robs them of all these things
There's a lot of human suffering behind the simple
statement ‘the leading cause of blindness.”
For information on how to participate in a related
clinical trial, call Michele Reg in the Department of Oph-
thalmology at 859/323—5868.

  
  
   
   
  
 
   
 
 
 
 
 
 
  
  
 
  
  
   
  

Ambati is trxing to lind answers to basic biological questions
about discascs of thc cw, spccilicallx—in two ongoing clinical
trialsithc origin and progression of agcrrclatcd macular

dcgcncration, the loading cause ol blindness in adults

 

 iabetes

“We have an epidemic of diabetes in
this country. and unless there‘s a lot
more attention paid to this disease. the
problem is just going to get worse."

This pronouncement comes from
Dennis Karounos. an associate profes-
sor in the Division of Endocrinology
and Molecular Medicine at UK and the
VA Medical Center, who says that the
risk is increasing for people with both
of the traditional forms of diabetes—
type I and type 2. Type 1 diabetes.
previously called insulin-dependent
diabetes mellitus orjuvenile-onset dia—
betes. may account for 5 to 10 percent
ofalldiagnosed casesofdiabetesType
2 diabetes. previously called non-insu-
lin-dependent diabetes mellitus or
adult—onset diabetes. is estimated to
account for about 90 to 95 percent of
all diagnosed cases.

Karounos explains “previously

“It used to be we'd hardly ever see a
child with type 2 diabetes: now 30
percentofchildren who have diabetes
have type 2. an alarmingly high num-
ber."

In 2001. 16.7 million Americans
were diagnosed with diabetes, ac-
cording to a study by the Centers for
Disease Control and Prevention pub-
lished in the Journal of the American
Medical Association last December. In
Kentucky in 2001, 6.6 percent of
people had been diagnosed with dia-
betes, a steady percentage climb
since 1994.

One reason for this increase.
Karounos says, is simple demograph-
ics. “Baby boomers are headed right

 

Dennis karounos is testing a \atcine to treat latent autoimmune diabetes, a tornrnon
but unfamiliar txpe of adulteonsct diabetes. In 2001, bf) percent of l\<‘i’tlLt( Ixians \\crc
diagnosed with diabetes, a stead\ percentage (limb sin< c 1004.

for their 60s and 705. when people become more prone to developing diabetes
because. when were older. the pancreas produces less insulin." he says.

Karounos came from Baylor University 12 years ago and is director ofthe diabetes
program at UK. He is currently focusing his work on what might be called a hybrid
type of diabetes—type 11/2, which is also called latent autoimmune diabetes in
adults (LADA‘).

“This is a common but unfamiliar type of adult—onset diabetes." he explains.
“LADA is a disease like type 1 diabetes in which the body‘s immune system attacks
and destroys insulin-producing cells in the pancreas. decreasing the body‘s ability
to produce insulin."

In testing a vaccine to treat LADA. Karounos is working with James Anderson. a
professor in the UK endocrinology and molecular medicine division who has been
researching diabetes for nearly 30 years. In this Phase II clinical trial, they are
teaming up with researchers at Washington University in St. Louis. and the universi-
ties of Colorado. Alabama. and Washington in Seattle.

“In order to tackle the problem of type 11/: diabetes clinically, we started looking
around at different therapies that are out there.“ Karounos says. “Lo and behold.
there was a group in Israel using an experimental drug that clearly improved insulin
secretion in people who‘d just developed type 1 diabetes.“

For this UK trial, Karounos initially screened. through a blood sample. potential
patients recently diagnosed with type 2 diabetes. He looked for antibodies that
indicate the autoimmune form of the disease. and if these antibodies were present,
and if the volunteers meet a couple of othercriteria. they were invited to join the trial,

The study is “double blind," which means neither the participant nor the
physician knows whether the experimental drug is being administered. The 20

 

  

participants will get eight injections
over two years. Half will get the vac—
cine: half will get an inactive shot.

As reported in the Lexington Hera/d-
Leader last November. Angela Blythe.
a UK pediatric nurse. was one of the
first two people enrolled in the UK
study. Her blood test found she has
the autoimmune form of the disease

“I hope I never have to get to the
point of needing insulin injections.“
she says. “The trial is a chance to test
something that could get rid of this so
that l never have to worry about it.“
About 80 percent of people who have
Blythe‘s type of diabetes eventually
need daily insulin shots. Karounossays.

The vaccine has exciting potential.
he says. If found to halt the progression
of diabetes by protecting the insulin—
producing cells of the pancreas. the
vaccine could be injected every three
to six months—“something like a tar-
geted allergy shot for pancreatic cells."
Karou nos says.

lfsuccessful.the vaccine could elimi—
nate or decrease the need for insulin
injections for up to 25 percent of people
with adult-onset diabetes—up to 3.2
million Americans.

“We‘re hoping to prevent people
from becoming dependent upon insu—
lin therapy.“ Karounos says. “Diabetes
typically affects a person's quality of
life. Right now. there’s no cure for dia—
betes. but with new drugs we will be
better able to control it.“

For information on how to participate
in this clinical trial. (all AK 5 .lr'embolrc
Research Group (12’ 859/25 74 058.

10

rotecting Human Subjects in Research

“There are a lot of players who share responsibility for the protection of human
subjects in research,” says Ada Sue Selwitz, who has shaped UK’s research
oversight activities since 1979.

it all begins with the researcher who is required by federal law to bring his or
her project before the appropriate institutional review board (UK has three lRBs
for medical research and one for non-medical projects). The lRB, a committee
of health-care professionals and community members, reviews the protocol to
look at the ethics ofthe research before deciding whether or not a trial can begin.
After the research protocol is approved, there are several points at which the IRB
continues to review the project: periodic review for continuing projects, review
when there is any modification to the protocol, and reviews when any unantici-
pated problems or adverse effects are reported.

Selwitz points to the peer review system for federally funded research as
another protection for clinical trial volunteers. “Even before a project is funded,
other scientists may be raising ethical concerns about a proposal," says Selwitz.

During the life of a clinical-trial project, the researcher is required to provide
periodic reports to the sponsor. The sponsor, in turn, is required to report any
problems to the FDA.

in a large clinical trial, another safeguard is the Data Safety Monitoring Board,
comprised of scientists who monitor a trial’s progress and who have the
authority to stop a trial if they have concerns about data as it comes in. If a trial
does not have a monitoring board, a researcher is required to set up a data safety
monitoring plan.

The Office of Human Research Protections, a federal lRB regulatory agency in
the Department of Health and Human Services, has the responsibility to en