Healthy VolunteersPhase 1NCT02363335
The Role of Phosphodiesterase Inhibitors in Incretin Secretion
A Phase 1 study testing Roflumilast/Sitagliptin, Sitagliptin and Roflumilast in people with Healthy Volunteers, run by National Institute on Aging (NIA) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Roflumilast/Sitagliptin, Sitagliptin and Roflumilast
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2015to 19 Sep 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
- Screening laboratory evaluations with no clinically significant abnormal results (minor deviations from normal lab results will be at the discretion of the principal investigator):
- fasting comprehensive metabolic panel
- complete blood count with differential and platelet
- thyroid function test (TSH)
- urine drug screen
Show all 12Show fewer
- Point of care urine pregnancy test (for women who are not surgically sterile)
- BMI < 30 (participants with BMI greater than or equal to 30 are excluded because obesity has been associated with attenuation in GLP-1 secretion.
- Have had a history of stable weight (maintained weight within +/- 5%) over the past year
- Have NOT participated in another clinical trial involving any pharmacologic agents within the past 30 days
- Able to complete an inform consent
- Agree to not participate in other clinical trials within the study period (at the discretion of the study investigator)
Who cannot join
- 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)
- History of anemia, or Hemoglobin < 12.5 mg/dL for men and < 11.5 mg/dL for women during screening visit
- Weight < 110 pounds (due to blood volume requirement)
- Evidence of illicit drug use
- History of substance abuse including marijuana within the past 6 months
- History of smoking any tobacco products within six months prior to screening
Show all 25Show fewer
- Alcohol intake > 30 grams (drink more than 2 beers per day OR equivalent amount of alcohol)
- History of Human Immunodeficiency Virus (HIV) infection
- History of active or chronic Hepatitis B and/or C infection
- History of psychiatric illnesses including major depressive disorder, schizophrenia, bipolar disorder
- Any lifetime history of suicide attempt
- History of any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the last year
- Any suicidal ideation of type 4 or 5 on the C-SSRS during any follow-up visits.
- Patient Health Questionnaire-9 (PHQ-9) score greater than or equal to 10 during screening visit or any follow-up study visits
- Generalized Anxiety Disorder-7 (GAD-7) score greater than or equal to 10 during screening visit or any follow-up visits
- History of pancreatitis
- History of liver or renal diseases
- History of gastrointestinal or endocrine disorders
- 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)
- History of coronary disease or clinically significant abnormalities on electrocardiogram
- History of seizures or other neurologic diseases
- 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
- Use of proton pump inhibitors (PPI s), i.e. Prilosec, Prevacid, Achiphex, Protonix, Nexium, Zegarid
- Women who are pregnant or nursing/breast-feeding a child
- Any medical history that, in the opinion of the investigator(s), may make participation of the subject in the study unsafe
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Aging, Clinical Research Unit
Baltimore, Maryland, 21224
About this study
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.
Read more
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:
- Roflumilast (Daliresp) 500 mcg pill; and 1 placebo pill
- Sitaglipitin (Januvia) 100 mg pill; and 1 placebo pill
- Roflumilast (Daliresp) 500 mcg pill; and Sitagliptin (Januvia) 100 mg pill
- 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.
Read the detailed description
Objectives and Specific Aims:
We plan to investigate whether phosphodiesterases are involved in the regulation of glucagon-like peptide-1 (GLP-1) secretion from L cells in humans. We hypothesize that: (1) phosphodiesterase-4D (PDE4D) inhibitor (roflumilast) enhance GLP-1 secretion from L cells; (2) PDE4D inhibitor (roflumilast) and DPP4 inhibitor (sitagliptin) have synergistic effect on increasing the amount of circulating active GLP-1.
Experimental Design and Methods:
Twenty healthy adults, age 21-55, will be recruited for this study. This is a randomized, double-blind, placebo-controlled cross-over study. Each subject will serve as his/her own control and each person will have four different study visits spaced about 3 weeks apart. During each visit, they will receive one of the following medications (oral route) in random order:
- Roflumilast (Daliresp) 500 mcg + Placebo
- Sitagliptin (Januvia) 100 mg + Placebo
- Roflumilast (Daliresp) 500 mcg + Sitagliptin (Januvia) 100 mg
- Placebo
A 10-hr mixed-meal test will be administered 1 hour after the medications and frequent blood-samplings will be done over 10 hours.
Medical Relevance and Expected Outcome:
Preliminary clinical data have shown that phosphodiesterase inhibitors improved glycemic control in type 2 diabetes, and pre-clinical animal data have shown that phosphodiesterase inhibitors enhanced GLP-1 secretion from L cells. The application of novel, pre-clinical findings to an understanding of human biology and pathobiology is of fundamental and critical importance. This study will give us a better understanding of the regulators of GLP-1 secretion in humans, and this new understanding may lead to new treatments for type 2 diabetes.
- Conditions
- Healthy Volunteers
- Being tested
- Placebo, Roflumilast/Sitagliptin, Sitagliptin, Roflumilast
- Keywords
- GLP-1, Phosphodiesterase Inhibitor, GIP
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
mixed meal
Roflumilast/SitagliptinOther
Both Roflumilast and Sitagliptin together
SitagliptinOther
This is already known to increase GLP-1 \& GIP secretion.
RoflumilastOther
This is already known to increase GLP-1 \& GIP secretion
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | randomized, double-blind, placebo-controlled cross-over study Receives: Other: Placebo |
| Roflumilast | Experimental | randomized, double-blind, placebo-controlled cross-over study Receives: Other: Placebo; Other: Roflumilast |
| Roflumilast/Sitaglip | Experimental | randomized, double-blind, placebo-controlled cross-over study Receives: Other: Placebo; Other: Roflumilast/Sitagliptin |
| Sitagliptin | Experimental | randomized, double-blind, placebo-controlled cross-over study Receives: Other: Placebo; Other: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
PDE4 inhibitor roflumilast enhances GLP-1 secretion from L cells.
GIP \& GLP-1 response to a mixed meal.
Measured: 1-10 hours after ingestion
Secondary outcomes (5)
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.
The hormones listed are measured by ELISA
Measured: 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.
The hormones listed are measured by ELISA
Measured: 1-10 hours after ingestion
3.PDE4 inhibitor roflumilast and DPP4 inhibitor sitagliptin have synergistic effect on elevating circulating active GIP levels.
GIP secretion in response to a mixed meal
Measured: 1-10 hours after ingestion
2.PDE4 inhibitor roflumilast enhances GIP secretion from K cells.
GIP secretion in response to a mixed meal
Measured: 1-10 hours after ingestion
1.PDE4 inhibitor roflumilast and DPP4 inhibitor sitagliptin have synergistic effect on elevating circulating active GLP-1 levels.
GLP-1 secretion in response to mixed meal
Measured: 1-10 hours after ingestion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2015 (estimated)
- Study start13 Feb 2015
- Primary completion19 Sep 2016
- Study completion19 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Chee W Chia, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02363335
- Sponsor's protocol ID
- 999915074
- Other IDs
- 15-AG-N074
- Status last verified
- 11 Mar 2026
- First submitted
- 13 Feb 2015
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: NIA IRP are in discussion and a plan has not been finalized.
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Phosphodiesterase Inhibitors in Incretin Secretion
- ClinicalTrials.gov ID
- NCT02363335
- Acronym / sponsor ID
- 999915074
- Conditions
- Healthy Volunteers
- Keywords
- GLP-1, Phosphodiesterase Inhibitor, GIP
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 13 Feb 2015
- Primary completion
- 19 Sep 2016 (actual)
- Study completion
- 19 Sep 2016 (actual)
- First posted
- 16 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Roflumilast (Daliresp) 500 mcg pill; and 1 placebo pill
- Sitaglipitin (Januvia) 100 mg pill; and 1 placebo pill
- Roflumilast (Daliresp) 500 mcg pill; and Sitagliptin (Januvia) 100 mg pill
- 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.
Detailed description
Objectives and Specific Aims:
We plan to investigate whether phosphodiesterases are involved in the regulation of glucagon-like peptide-1 (GLP-1) secretion from L cells in humans. We hypothesize that: (1) phosphodiesterase-4D (PDE4D) inhibitor (roflumilast) enhance GLP-1 secretion from L cells; (2) PDE4D inhibitor (roflumilast) and DPP4 inhibitor (sitagliptin) have synergistic effect on increasing the amount of circulating active GLP-1.
Experimental Design and Methods:
Twenty healthy adults, age 21-55, will be recruited for this study. This is a randomized, double-blind, placebo-controlled cross-over study. Each subject will serve as his/her own control and each person will have four different study visits spaced about 3 weeks apart. During each visit, they will receive one of the following medications (oral route) in random order:
- Roflumilast (Daliresp) 500 mcg + Placebo
- Sitagliptin (Januvia) 100 mg + Placebo
- Roflumilast (Daliresp) 500 mcg + Sitagliptin (Januvia) 100 mg
- Placebo
A 10-hr mixed-meal test will be administered 1 hour after the medications and frequent blood-samplings will be done over 10 hours.
Medical Relevance and Expected Outcome:
Preliminary clinical data have shown that phosphodiesterase inhibitors improved glycemic control in type 2 diabetes, and pre-clinical animal data have shown that phosphodiesterase inhibitors enhanced GLP-1 secretion from L cells. The application of novel, pre-clinical findings to an understanding of human biology and pathobiology is of fundamental and critical importance. This study will give us a better understanding of the regulators of GLP-1 secretion in humans, and this new understanding may lead to new treatments for type 2 diabetes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placeborandomized, double-blind, placebo-controlled cross-over study |
| Roflumilast | Experimental | Other: Placebo, Other: Roflumilastrandomized, double-blind, placebo-controlled cross-over study |
| Roflumilast/Sitaglip | Experimental | Other: Placebo, Other: Roflumilast/Sitagliptinrandomized, double-blind, placebo-controlled cross-over study |
| Sitagliptin | Experimental | Other: Placebo, Other: Sitagliptinrandomized, double-blind, placebo-controlled cross-over study |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
Key exclusion criteria (25 listed)
- 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)
- History of anemia, or Hemoglobin < 12.5 mg/dL for men and < 11.5 mg/dL for women during screening visit
- Weight < 110 pounds (due to blood volume requirement)
- Evidence of illicit drug use
- History of substance abuse including marijuana within the past 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebomixed meal | Other | Placebo, Roflumilast, Roflumilast/Sitaglip, Sitagliptin |
| Roflumilast/SitagliptinBoth Roflumilast and Sitagliptin together | Other | Roflumilast/Sitaglip |
| SitagliptinThis is already known to increase GLP-1 \& GIP secretion. | Other | Sitagliptin |
| RoflumilastThis is already known to increase GLP-1 \& GIP secretion | Other | Roflumilast |
Primary outcome
PDE4 inhibitor roflumilast enhances GLP-1 secretion from L cells.
Time frame: 1-10 hours after ingestion
GIP \& GLP-1 response to a mixed meal.
5 secondary outcomes
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
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
3.PDE4 inhibitor roflumilast and DPP4 inhibitor sitagliptin have synergistic effect on elevating circulating active GIP levels.
Time frame: 1-10 hours after ingestion
2.PDE4 inhibitor roflumilast enhances GIP secretion from K cells.
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Individual participant dataSharing planned: Undecided. NIA IRP are in discussion and a plan has not been finalized.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chee W Chia, M.D. principal investigator
National Institute on Aging (NIA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Roflumilast/Sitagliptin, Sitagliptin and Roflumilast in people with Healthy Volunteers, run by National Institute on Aging (NIA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PDE4 inhibitor roflumilast enhances GLP-1 secretion from L cells. (time frame: 1-10 hours after ingestion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.