The Role of Phosphodiesterase Inhibitors in Incretin Secretion

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2024
• Main ID: NCT02363335
• Date of registration: 13/02/2015
• Prospective Registration: Yes
• Primary sponsor: National Institute on Aging (NIA)
• Public title: The Role of Phosphodiesterase Inhibitors in Incretin Secretion
• Scientific title: The Role of Phosphodiesterase Inhibitors in Incretin Secretion
• Date of first enrolment: February 13, 2015
• Target sample size: 29
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02363335
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Factorial Assignment. Primary purpose: Basic Science. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Josephine M Egan, M.D.
• Affiliation: National Institute on Aging (NIA)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

1. Age 21-55 (Age restriction is used to remove age as a confounding factor because
(beta) cells function and insulin resistance tend to deteriorate with age and may
affect GLP-1 and GIP levels.

2. Screening laboratory evaluations with no clinically significant abnormal results
(minor deviations from normal lab results will be at the discretion of the
principal investigator):

1. fasting comprehensive metabolic panel

2. complete blood count with differential and platelet

3. thyroid function test (TSH)

4. urine drug screen

5. Point of care urine pregnancy test (for women who are not surgically
sterile)

3. BMI < 30 (participants with BMI greater than or equal to 30 are excluded because
obesity has been associated with attenuation in GLP-1 secretion.

4. Have had a history of stable weight (maintained weight within +/- 5%) over the
past year

5. Have NOT participated in another clinical trial involving any pharmacologic
agents within the past 30 days

6. Able to complete an inform consent

7. Agree to not participate in other clinical trials within the study period (at the
discretion of the study investigator)

EXCLUSION CRITERIA:

1. FPG greater than or equal to 100 mg/dl or 2-hr OGTT greater than or equal to 140 mg/dL
(evidence of glucose intolerance or diabetes)

2. History of anemia, or Hemoglobin < 12.5 mg/dL for men and < 11.5 mg/dL for women
during screening visit

3. Weight < 110 pounds (due to blood volume requirement)

4. Evidence of illicit drug use

5. History of substance abuse including marijuana within the past 6 months

6. History of smoking any tobacco products within six months prior to screening

7. Alcohol intake > 30 grams (drink more than 2 beers per day OR equivalent amount of
alcohol)

8. History of Human Immunodeficiency Virus (HIV) infection

9. History of active or chronic Hepatitis B and/or C infection

10. History of psychiatric illnesses including major depressive disorder, schizophrenia,
bipolar disorder

11. Any lifetime history of suicide attempt

12. History of any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity
Rating Scale (C-SSRS) in the last year

13. Any suicidal ideation of type 4 or 5 on the C-SSRS during any follow-up visits.

14. Patient Health Questionnaire-9 (PHQ-9) score greater than or equal to 10 during
screening visit or any follow-up study visits

15. Generalized Anxiety Disorder-7 (GAD-7) score greater than or equal to 10 during
screening visit or any follow-up visits

16. History of pancreatitis

17. History of liver or renal diseases

18. History of gastrointestinal or endocrine disorders

19. History of malignancy (unless P.I. determines that there is no impact of the prior
malignancy on study outcomes, i.e. basal cell skin cancer)

20. History of coronary disease or clinically significant abnormalities on
electrocardiogram

21. History of seizures or other neurologic diseases

22. History of glucocorticoid use (over one month) or other immunosuppressive agents
(any), i.e. Imuran, Neoral, Sandimmune, SangCya, basiliximab (Simulect), daclizumab
(Zenapax), muromonab (Orthocolone OKT(3)) prednisone (Deltasone, Orasone) within the
past six months

23. Use of proton pump inhibitors (PPI s), i.e. Prilosec, Prevacid, Achiphex, Protonix,
Nexium, Zegarid

24. Women who are pregnant or nursing/breast-feeding a child

25. Any medical history that, in the opinion of the investigator(s), may make
participation of the subject in the study unsafe



Age minimum: 21 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Healthy Volunteers

Intervention(s)

Other: Sitagliptin

Other: Placebo

Other: Roflumilast

Other: Roflumilast/Sitagliptin

Primary Outcome(s)

PDE4 inhibitor roflumilast enhances GLP-1 secretion from L cells. [Time Frame: 1-10 hours after ingestion]

Secondary Outcome(s)

2.PDE4 inhibitor roflumilast enhances GIP secretion from K cells. [Time Frame: 1-10 hours after ingestion]

4.PDE4 inhibitor roflumilast has an effect on glucose metabolism involving plasma glucose, insulin, ghrelin, glucagon, pancreatic polypeptide, C-peptide and fibroblast growth factor (FGF) 19, 21, 23. [Time Frame: 1-10 hours after ingestion]

5.PDE4 inhibitor roflumilast and DPP4 inhibitor sitagliptin have synergistic effect on glucose metabolism involving plasma glucose, insulin, ghrelin, glucagon, pancreatic polypeptide, C-peptide and fibroblast growth factor (FGF) 19, 21, 23. [Time Frame: 1-10 hours after ingestion]

1.PDE4 inhibitor roflumilast and DPP4 inhibitor sitagliptin have synergistic effect on elevating circulating active GLP-1 levels. [Time Frame: 1-10 hours after ingestion]

3.PDE4 inhibitor roflumilast and DPP4 inhibitor sitagliptin have synergistic effect on elevating circulating active GIP levels. [Time Frame: 1-10 hours after ingestion]

Secondary ID(s)

15-AG-N074

999915074

Source(s) of Monetary Support

Please refer to primary and secondary sponsors