- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01862029
Effects of Roflumilast on Insulin and Blood Sugar Levels in Prediabetic Overweight and Obese Individuals
An Exploratory Study to Evaluate the Effects of Roflumilast on Insulin Sensitivity and Metabolic Parameters in Prediabetic Overweight and Obese Individuals
Background:
- Roflumilast is a drug used to treat chronic obstructive pulmonary disease (COPD). It is designed to help reduce lung inflammation. However, during testing, roflumilast also appeared to reduce high blood sugar levels in people with COPD and type 2 diabetes. Other tests showed that roflumilast also improved blood sugar levels in people who only had type 2 diabetes. Researchers want to see how roflumilast affects insulin and blood sugar levels in overweight or obese people who are not diabetic, but who have high blood sugar levels.
Objectives:
- To see how well roflumilast improves blood sugar and insulin levels in prediabetic overweight or obese individuals.
Eligibility:
- Individuals between 30 to 65 years old who are overweight or obese (body mass index of 24.9 to 39.9 kg/m2) and have elevated blood sugar levels.
Design:
- This study will last approximately 8 weeks. Participants will have approximately five study visits over about 7 weeks. Two of these visits will be overnight inpatient stays.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. They will also have a 3-day diet and exercise assessment with a dietitian.
- In Week 1, participants will have a special diet for 2 days to keep their regular weight. They will then have a 2-day inpatient stay. During their stay, they will have multiple tests, including blood sugar tests and full body scans. They may provide a fat and muscle tissue biopsy sample. They will then receive the study drug to take during the study.
- In Week 2, participants will repeat the diet study from the screening visit. They will receive a different dose of the study drug.
- In Week 3, participants will review their diet results and have blood and urine tests.
- In Week 5, participants will repeat the diet and exercise study from the screening visit.
- In Week 6, participants will repeat the inpatient studies and tests from Week 1.
In the last week, participants will have a final follow-up visit.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center, 9000 Rockville Pike
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
- INCLUSION CRITERIA:
- Adult, weight- and diet-stable men and women in good general health with no significant underlying illnesses and normal or clinically insignificant results (medical histories, laboratory profiles, physical examination, and electrocardiograms),
- Women must be non-pregnant or post-menopausal, or women of childbearing potential must be non-lactating and using an effective form of birth control during and for 30 days after the study period (partner's use of condoms or partner's vasectomy is not an acceptable contraception method for this study),
- Must be 30 - 65 years of age, inclusive
- Body Mass Index (BMI) > 24.9 and < 39.5 kg/m(2) with a stable (plus-minus 2.5 kg) weight for the last 6 months by history,
- Pre-diabetes, as defined by a fasting blood glucose of greater than 100 mg/dL and less than 126 mg/dL and/or A1C equal or greater than 5.7 and less than or equal to 6.5 %
- Subjects must be able to understand the protocol and provide written informed consent.
EXCLUSION CRITERIA:
- Women will be excluded from our study if they are pregnant, breastfeeding, or if they plan to become pregnant prior to the end of the study,
- Cannot be on any medications including multivitamins or nutritional supplements that in the investigator s opinion will affect insulin sensitivity
- Currently taking systemic corticosteroids, insulin, or anticoagulants, anxiolytics, ketoconazole, erythromycin, cimetidine, enoxacin, strong CYP 3A4/1A2 inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin), birth control pills containing gestodene and ethinyl estradiol, use food supplements that cannot be discontinued, or any other medication that the investigators deem a contraindication.
- AST or ALT > 3 times the upper normal limit
- Hepatitis B antigen, HIV or C positive antibody tests,
- Liver disease, pulmonary disease, renal insufficiency, , (serum creatinine > 1.5mg/dl), coronary heart disease, heart failure (New York Heart Association heart failure Class III or IV), peripheral vascular disease, coagulopathy.
- History of or current diagnosis of major depressive disorder, or history of or current diagnosis of other psychiatric disorders that in the opinion of the investigator would make participant unsafe for the participant.
- Currently being treated for any form of cancer or have a history of cancer, that in the investigator s judgment would not make the participant a candidate for the study for safety or scientific reasons.
- Claustrophobic,
- On a weight loss program with ongoing weight loss, or a history of eating disorders. Actively using tobacco products or have used tobacco products within last year (>3 cigarettes/day), regular alcoholic beverage intake of more than two drinks per day. Subjects with any condition that would have made them, in the opinion of the principal investigator (PI), unsuitable for the study.
- Subjects with a contraindication for the ultrasound contrast agent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Roflumilast
|
Selective phosphodiesterase 4 (PDE4) inhibitor
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Insulin Sensitivity- Pre-roflumilast
Time Frame: Baseline
|
Our primary outcome measure is the change in peripheral insulin sensitivity.
The hyperinsulinemic euglycemic clamp procedure's M value, which was obtained before the subjects began roflumilast, was used to assess the primary outcome.
|
Baseline
|
Change in Insulin Sensitivity - Post-roflumilast
Time Frame: 6 weeks
|
Our primary outcome measure is the change in peripheral insulin sensitivity.
The hyperinsulinemic euglycemic clamp procedure's M value, which was obtained post-roflumilast, was used for this primary outcome assessment.
|
6 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Jay H Chung, M.D., National Heart, Lung, and Blood Institute (NHLBI)
Publications and helpful links
General Publications
- Wouters EF, Bredenbroker D, Teichmann P, Brose M, Rabe KF, Fabbri LM, Goke B. Effect of the phosphodiesterase 4 inhibitor roflumilast on glucose metabolism in patients with treatment-naive, newly diagnosed type 2 diabetes mellitus. J Clin Endocrinol Metab. 2012 Sep;97(9):E1720-5. doi: 10.1210/jc.2011-2886. Epub 2012 Jun 20.
- Yajima H, Komatsu M, Schermerhorn T, Aizawa T, Kaneko T, Nagai M, Sharp GW, Hashizume K. cAMP enhances insulin secretion by an action on the ATP-sensitive K+ channel-independent pathway of glucose signaling in rat pancreatic islets. Diabetes. 1999 May;48(5):1006-12. doi: 10.2337/diabetes.48.5.1006.
- Millesi H. Peripheral nerve surgery today: turning point or continuous development? J Hand Surg Br. 1990 Aug;15(3):281-7. doi: 10.1016/0266-7681_90_90004-n. No abstract available.
- Muo IM, MacDonald SD, Madan R, Park SJ, Gharib AM, Martinez PE, Walter MF, Yang SB, Rodante JA, Courville AB, Walter PJ, Cai H, Glicksman M, Guerrieri GM, Ben-Dor RR, Ouwerkerk R, Mao S, Chung JH. Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight/obesity involve age-associated fat mass loss - results of an exploratory study. Diabetes Metab Syndr Obes. 2019 May 27;12:743-759. doi: 10.2147/DMSO.S182953. eCollection 2019.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 130123
- 13-H-0123
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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