The Role of Phosphodiesterase Inhibitors in Incretin Secretion

Summary

Background:

The drug Roflumilast (Daliresp) is used to treat Chronic Obstructive Pulmonary Disease (COPD). COPD is a lung disease that makes it difficult to breathe. Studies have shown that this drug decreased the blood sugar of people with type 2 diabetes. Sitagliptin (Januvia) is a medication presently used to treat diabetes. Researchers think that both of these drugs may decrease blood sugar by causing an increase in the hormone GLP-1.This hormone is secreted in the small intestines and stomach and is also known as an incretin. Researchers want to study how these drugs affect blood sugar, insulin, and other hormones in the blood.

Objectives:

* To study the effects of Roflumilast (Daliresp) and Sitagliptin (Januvia) on blood sugar and insulin.
* To better understand GLP-1 and other gut hormones. This may lead to new treatments for type 2 diabetes.

Eligibility:

* Healthy volunteers age 21 55.
* Body Mass Index (BMI) less than 30

Design:

-This study will require one screening visit and four study visits, scheduled about 3-weeks apart.

Screening visit requires participants to arrive after fasting for 10 hours and have the following:

* Medical history, physical exam, height, weight, blood pressure measurements and blood and urine tests.
* A 2-hour oral glucose tolerance test (OGTT). Participants will drink an orange-flavored drink containing 75 grams of sugar (300 calories). A blood sample will be taken prior to drinking the beverage and 2-hours later.
* An electrocardiogram (EKG) to measure the electrical activity of the heart.
* Questionnaires about risk for depression or suicide.

Study visits 1to 4:

* Participants will arrive the evening prior and blood work will be done to confirm eligibility. They will not eat or drink anything except water starting at 8:00 p.m.
* About 6:30 a.m. the following day, an I.V. (small plastic tube) will be placed in an arm vein and used to take 20 blood samples over a period of about 11 hours.
* Participants will receive one of the following study medication/placebo groupings in random order:

1. Roflumilast (Daliresp) 500 mcg pill; and 1 placebo pill
2. Sitaglipitin (Januvia) 100 mg pill; and 1 placebo pill
3. Roflumilast (Daliresp) 500 mcg pill; and Sitagliptin (Januvia) 100 mg pill
4. 2 placebo pills
* One hour later, they will have a 10-hour mixed meal test (MMT). They will be asked to drink a nutritional shake (Ensure Plus). Blood samples will be taken over the next 10 hours to measure blood sugar, insulin and other hormones. At the end of the test, they will be given a meal.
* Participants will answer questions about side effects and symptoms. They will receive a follow-up phone call within 10 days.

Conditions

• Healthy Volunteers

Interventions

OTHER

Placebo

mixed meal

OTHER

Roflumilast/Sitagliptin

Both Roflumilast and Sitagliptin together

OTHER

Sitagliptin

This is already known to increase GLP-1 \& GIP secretion.

OTHER

Roflumilast

This is already known to increase GLP-1 \& GIP secretion

Sponsors & Collaborators

• National Institute on Aging (NIA)

  lead NIH

Principal Investigators

• Chee W Chia, M.D. · National Institute on Aging (NIA)

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

FACTORIAL

Eligibility

Min Age

21 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-02-13

Primary Completion

2016-09-19

Completion

2016-09-19

FDA Drug

Yes

Countries

• United States

Study Locations