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Vanderbilt Medical Center doctors test inhaled form of insulin in clinical trials

Feb. 19, 2004, 8:55 AM

Vanderbilt University Medical Center researchers are studying a new
inhaled form of insulin in three separate clinical trials. If proven
effective the new form of insulin, which is delivered to patients as an
aerosolized powder via the lungs, could cut in half the number of
insulin injections for a certain population of diabetics.

With the disease fast reaching epidemic proportions, diabetes currently
affects over 18 million people in the United States alone. An estimated
60 million Americans suffer from elevated glucose levels, a
pre-diabetic condition indicating numbers of those affected by the
disease will explode in the coming years.

Diabetics who receive insulin typically self-administer several shots
daily. Type 1 diabetics typically take one dose of long-acting insulin
in the evening, accompanied by several doses of short-acting insulin
throughout the day. Insulin-dependent type 2 diabetics often follow a
similar insulin regimen.

Some new types of quick-acting insulin, developed in the mid-1990’s,
can be prescribed for either shortly before, or in some instances even
immediately after meals to maintain blood sugar levels after food
consumption.

A new inhaled, rapid-acting, dry-powder form of insulin, currently
called Exubera, is being tested to replace injections of short-acting
insulin.

"All preliminary studies done elsewhere show inhaled insulin is
effective," said Dr. Stephen Davis, the Rudolph H. Kampmeier professor
of Medicine, chief of the Division of Diabetes, Endocrinology and
Metabolism, and principal investigator on one of VUMC’s three trials of
Exubera. "Additionally, the patient satisfaction scores from these
studies are very high."

For diabetics who receive insulin up to four times a day, that can
represent as many as 1460 injections a year. And that number doesn’t
include the number of skin pricks diabetics must endure to draw blood
samples for monitoring blood sugar levels. Some diabetics may
require more than four daily insulin injections.

Kathleen Hayslip, a 57-year-old insulin-dependent type II diabetic who
also suffers from asthma, thinks having a more convenient way to
receive the drug would be a tremendous benefit. While saying that
living with diabetes isn’t the worst thing in the world, Hayslip
resents how labor-intensive it is to be insulin-dependent, and says the
disease can rob diabetics of some of the spontaneity of
life.

"I would be more prone to take the dose of insulin I need at the
appropriate time if it was easier to do," Hayslip said. "I hate to
admit it, but I don’t always do that."

Hayslip cites difficulties diabetics face such as having to calculate
and inject insulin doses ahead of mealtime. "If I’m at a restaurant and
decide to have something different to eat than I originally calculated,
then I have to consider my insulin," she said. "When I’m around family
or close friends I’m OK, otherwise in a social setting I feel
self-conscious about injecting. Then there can be sanitary issues while
out in public with trying to find a clean, private place to inject."

Other than a cure for the disease, the holy grail of diabetes research
is the ongoing search for more effective, less painful, methods to
administer insulin and monitor blood sugar levels.

According to Dr. John Murray, associate professor of Medicine and
Pharmacology and the Elizabeth and John Murray associate professor of
Asthma, Sinus and Allergy Program, who is principal investigator on two
of VUMC’s inhaled insulin studies, the concept of delivering inhaled
insulin to diabetics through the lungs has been around for decades.

"The whole concept of nebulized, or airway-delivered, insulin has been
around for 75 years. In addition to insulin delivered by injection,
insulin was originally delivered by inhalation shortly after its
discovery back in the 1920’s," said Murray. "There was a lot of
variation in delivery, such as not being able to control the dose back
then, so it never went anywhere."

Murray says that drug companies began to look at delivering insulin by
inhalation again in the 1980’s and 1990’s, which led to the development
of Exubera and new nebulizer technology to administer accurate dosing.

The Diabetes Complication Control Trial (DCCT), a landmark national
trial headed by former VUMC faculty member Dr. Oscar Crofford,
professor of Medicine emeritus, forever changed the way diabetics are
taught to manage their disease. The DCCT led to proof that diabetics
who receive insulin several times daily, and most closely manage their
blood sugar levels day-in and day-out, suffer far fewer serious
complications associated with diabetes.

Emphasis is now placed on tight control over blood sugar levels, which
is achieved by exactly when, and how much, insulin is delivered.
Therefore there is an ever-greater need for more convenient methods of
delivery.

"Diabetics need to take insulin before they eat to appropriately manage
blood glucose levels. One of the problems with this approach is that it
can be inconvenient for people to inject themselves midday," Murray
said. "Another problem is that diabetics usually need to take their
injections before eating to reach peak level. That can be inconvenient,
or hard to remember. One of the advantages of Exubera is that it is as
fast as quick-acting insulin getting into a person’s
system."

The inhaled form of insulin now being tested at VUMC in late Phase III
trials is close to gaining broad-market FDA approval. But one of the
remaining questions is the effectiveness of this form of insulin in
patient populations who suffer from respiratory complications.

Murray’s two inhaled insulin studies, being conducted through the
Asthma Sinus Allergy Prevention (ASAP) Research program, are seeking
oral medication-dependent or insulin-dependent diabetic adults, ages
18-75, who suffer from either COPD (chronic obstructive pulmonary
disease including chronic bronchitis and emphysema) or asthma.

Both of Murray’s studies will look at several variables- whether
insulin control can be maintained over time, whether fluctuations in
the patient’s pulmonary disease alters insulin control, and whether
giving insulin through the lungs in this patient population might have
an adverse effect on the lungs themselves.

"One of the questions is that if you’re giving insulin by inhalation,
are you going to have variability in absorption from a normal person to
someone with lung disease, and is that variability going to change with
the state of the disease?," Murray said.

VUMC’s other inhaled insulin study currently under way is being
conducted through the Division of Diabetes, Endocrinology and
Metabolism by Dr. Stephen Davis and Dr. Deanna Aftab Guy, instructor of
Pediatrics in the Division of Pediatric Endocrinology.

Davis and Aftab Guy are seeking adult patients with type 2 diabetes who
are currently on oral medications, and having difficulty maintaining
appropriate blood sugar levels.

"We are looking for diabetic adults, ages 35-80, currently on two oral
medications with an average blood sugar level of 180, and whose
diabetes is poorly controlled," said Aftab Guy. "Participants must also
be less than 130 pounds overweight."

Ideal participants for the adult type 2 study would be at the point in
the disease process their diabetes will soon require switching from
oral medications to insulin.

"We think inhaled insulin will be particularly appealing, especially to
type 2 diabetics," said Davis. "Over fifty percent of type 2 diabetics
eventually need to receive insulin. Most people would prefer not to
inject it."

All three studies are conducted on an outpatient basis. Participants
will receive a thorough history and physical prior to enrollment.
Participants in Murray’s two studies will undergo a thorough evaluation
of lung function and will have pulmonary function closely monitored
throughout the study. All participants will receive free medications
and blood glucose monitoring supplies for the duration of the studies.

"We are very hopeful, and early results with this method of insulin delivery are very encouraging," said Davis.

For information about the asthma or COPD & inhaled insulin studies,
please contact ASAP Research at 936-5764. For information about the
adult type 2 inhaled insulin study contact Dr. Deanna Aftab Guy at
936-1824.

Media contact: John Howser (615) 322-4747
john.howser@vanderbilt.edu

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