Healthy VolunteersPhase 1NCT01517100
The Role of Endocannabinoids in Insulin Production and Action
A Phase 1 study testing Nabilone, CP-945,598 and hyperglycemic clamp in people with Healthy Volunteers, run by National Institute on Aging (NIA) at 1 site in United States.
Trial summary
Background: The endocannabinoid system is involved in different body functions and processes. It helps regulate appetite and mood, and sends signals to the nervous system. It may also be involved in how the body produces insulin during digestion. 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?
- Nabilone, CP-945,598 and hyperglycemic clamp
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2012to 6 Oct 2014
- 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
- Healthy men only
- (We want to study men because the magnitude of acute insulin response for men and women is different. In addition, as women may become pregnant in the course of the study, and since this is a physiology study only, and not one related to treatments, we want to remove any confounders and lessen any chance of drop-out.)
- Age 21-55 (Age restriction is used to remove age as a confounding factor because Beta cells function tends to deteriorate and first phase secretion becomes less defined with age.
- 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
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- thyroid function test (TSH, free T4)
- urinalysis
- urine drug screen
- BMI less than 30 (Men with BMI greater than or equal to 30 are excluded because obesity has been associated with altered beta cell function.
- 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
- Women
- FPG greater than or equal to 100 mg/dl or 2-hr OGTT greater than or equal to 140 mg/dL
- 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
- Alcohol intake greater than 30 grams (drink more than 2 beers per day OR equivalent amount of alcohol)
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- History of Human Immunodeficiency Virus (HIV) infection
- History of active or chronic Hepatitis B and/or C infection
- History of malignancy
- History of coronary disease
- History of seizures or other neurologic diseases
- History of psychiatric illnesses including major depressive disorder, schizophrenia, bipolar disorder
- Any lifetime history of suicide attempt
- History of suicidal behavior in the last year
- Any suicidal behavior during any follow-up visits
- 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 liver or renal diseases
- History of gastrointestinal or endocrine disorders
- History of glucocorticoid use (over one month) or other immunosuppressive agents (any)
- Any condition or non-removable device contraindicated for MRI (pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments, or history of working as a welders or metal worker)
- Any medical history that, in the opinion of the investigator(s), will 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
Official title: The Roles of Endocannabinoids in Insulin Secretion and Action
Background:
- The endocannabinoid system is involved in different body functions and processes. It helps regulate appetite and mood, and sends signals to the nervous system. It may also be involved in how the body produces insulin during digestion. Researchers want to test two drugs that work on the endocannabinoid system: nabilone and CP-945,598. These drugs may be able to affect insulin levels in the blood. This information may suggest possible new treatments for people with diabetes.
Read more
Objectives:
- To study how the endocannabinoid system is involved in insulin production and action.
Eligibility:
- Healthy men between 21 and 55 years of age.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood and urine samples. They will also have imaging studies to test their brain responses, especially to food-related cues. Some participants will also have a study visit to test their insulin resistance levels.
- Participants will have four separate study visits 6 weeks apart. They will keep a food diary before each visit. At each visit, they will have one of the following combinations of drugs:
- Double placebo
- Placebo and nabilone
- Placebo and low dose of CP-945,598
- Placebo and high dose of CP-945,598.
- Participants will have follow-up visits 1 week after each study visit. Blood samples will be taken....
Read the detailed description
Objectives and Specific Aims:
We plan to investigate whether the endocannabinoid system is involved in the regulation of insulin secretion from Beta cells and in the modulation of insulin action in peripheral tissues in humans. We hypothesize that cannabinoid receptor 1 (CB1R) antagonist CP-945,598 will increase insulin secretion from Beta cells and improve insulin sensitivity in peripheral tissues while cannabinoid receptor (CBR) agonist nabilone will decrease insulin secretion from Beta cells and worsen insulin sensitivity in peripheral tissues. Moreover, we will investigate the brain s control over the initial phase of insulin secretion (cephalic insulin response) and the effect of central cannabinoid receptors.
Experimental Design and Methods:
Twenty healthy men, 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 own control and each person will have four different intervention visits spaced at least 6 weeks apart. During each visit, they will receive one of the following medications in random order: placebo, nabilone 2 mg, CP-945,598 15 mg, or CP-945,598 45 mg. A sequential hyperglycemic-euglycemic clamp procedure and a 3-hr oral glucose tolerance test will be used to study the effect of CP-945,598 and nabilone on insulin secretion and insulin action in healthy men. To identify brain areas involved in cephalic insulin response, a functional MRI will be used to assess brain activation in response to food images in association with frequent blood sampling.
Medical Relevance and Expected Outcome:
Based on our pre-clinical animal data, CB1R antagonist enhances insulin secretion and action in response to glucose while CBR agonist virtually shuts off insulin secretion and worsens insulin action in response to glucose. 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 insulin secretion from Beta cells and insulin sensitivity in humans, and this new understanding is of importance to finding new treatments for type 2 diabetes.
- Conditions
- Healthy Volunteers
- Being tested
- Nabilone, CP-945,598, hyperglycemic clamp, euglycemic-hyperinsulinemic clamp
- Keywords
- Glucose, Insulin Secretion, Insulin Action, Endocannabinoids, Insulin, Metabolism
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NabiloneOther
CB agonist
CP-945,598Drug
Cannabinoid Receptor 1 antagonist
hyperglycemic clampOther
assesses beta cell response
euglycemic-hyperinsulinemic clampOther
measures insulin sensitivity
NabiloneOther
cannabinoid receptor agonist
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in insulin sensitivity.
This study will give us a better understanding of the regulators of insulin secretion from B cells and insulin sensitivity in humans and this new understanding is of importance to finding new treatments for type 2 diabetes
Measured: CB1R antagonist CP-945,598 will enhance while CR receptor agonist nabilone will suppress first phase insulin response fromB cells in humans
Secondary outcomes (1)
Changes in insulin and other hormones and the brain response to picture of food items evidenced by functional MRI of the brain.
Measured: 90 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study start5 Jan 2012
- Primary completion6 Oct 2014
- Study completion6 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 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
- NCT01517100
- Sponsor's protocol ID
- 999912018
- Other IDs
- 12-AG-N018
- Status last verified
- 11 Mar 2026
- First submitted
- 24 Jan 2012
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The NIA IRP is discussing the plan to make IPD available. A final decision has not been made.
Publications
Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus. Diabetologia. 2001 Aug;44(8):929-45. doi: 10.1007/s001250100580.
PubMed 11484070Straub SG, Sharp GW. Hypothesis: one rate-limiting step controls the magnitude of both phases of glucose-stimulated insulin secretion. Am J Physiol Cell Physiol. 2004 Sep;287(3):C565-71. doi: 10.1152/ajpcell.00079.2004.
PubMed 15308461Elahi D, Muller DC, McAloon-Dyke M, Tobin JD, Andres R. The effect of age on insulin response and glucose utilization during four hyperglycemic plateaus. Exp Gerontol. 1993 Jul-Oct;28(4-5):393-409. doi: 10.1016/0531-5565(93)90066-m.
PubMed 8224037
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Roles of Endocannabinoids in Insulin Secretion and Action
- ClinicalTrials.gov ID
- NCT01517100
- Acronym / sponsor ID
- 999912018
- Conditions
- Healthy Volunteers
- Keywords
- Glucose, Insulin Secretion, Insulin Action, Endocannabinoids, Insulin, Metabolism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 5 Jan 2012
- Primary completion
- 6 Oct 2014 (actual)
- Study completion
- 6 Oct 2014 (actual)
- First posted
- 25 Jan 2012 (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 endocannabinoid system is involved in different body functions and processes. It helps regulate appetite and mood, and sends signals to the nervous system. It may also be involved in how the body produces insulin during digestion. Researchers want to test two drugs that work on the endocannabinoid system: nabilone and CP-945,598. These drugs may be able to affect insulin levels in the blood. This information may suggest possible new treatments for people with diabetes.
Objectives:
- To study how the endocannabinoid system is involved in insulin production and action.
Eligibility:
- Healthy men between 21 and 55 years of age.
Design:
- Participants will be screened with a physical exam and medical history. They will provide blood and urine samples. They will also have imaging studies to test their brain responses, especially to food-related cues. Some participants will also have a study visit to test their insulin resistance levels.
- Participants will have four separate study visits 6 weeks apart. They will keep a food diary before each visit. At each visit, they will have one of the following combinations of drugs:
- Double placebo
- Placebo and nabilone
- Placebo and low dose of CP-945,598
- Placebo and high dose of CP-945,598.
- Participants will have follow-up visits 1 week after each study visit. Blood samples will be taken....
Detailed description
Objectives and Specific Aims:
We plan to investigate whether the endocannabinoid system is involved in the regulation of insulin secretion from Beta cells and in the modulation of insulin action in peripheral tissues in humans. We hypothesize that cannabinoid receptor 1 (CB1R) antagonist CP-945,598 will increase insulin secretion from Beta cells and improve insulin sensitivity in peripheral tissues while cannabinoid receptor (CBR) agonist nabilone will decrease insulin secretion from Beta cells and worsen insulin sensitivity in peripheral tissues. Moreover, we will investigate the brain s control over the initial phase of insulin secretion (cephalic insulin response) and the effect of central cannabinoid receptors.
Experimental Design and Methods:
Twenty healthy men, 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 own control and each person will have four different intervention visits spaced at least 6 weeks apart. During each visit, they will receive one of the following medications in random order: placebo, nabilone 2 mg, CP-945,598 15 mg, or CP-945,598 45 mg. A sequential hyperglycemic-euglycemic clamp procedure and a 3-hr oral glucose tolerance test will be used to study the effect of CP-945,598 and nabilone on insulin secretion and insulin action in healthy men. To identify brain areas involved in cephalic insulin response, a functional MRI will be used to assess brain activation in response to food images in association with frequent blood sampling.
Medical Relevance and Expected Outcome:
Based on our pre-clinical animal data, CB1R antagonist enhances insulin secretion and action in response to glucose while CBR agonist virtually shuts off insulin secretion and worsens insulin action in response to glucose. 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 insulin secretion from Beta cells and insulin sensitivity in humans, and this new understanding is of importance to finding new treatments for type 2 diabetes.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- (We want to study men because the magnitude of acute insulin response for men and women is different. In addition, as women may become pregnant in the course of the study, and since this is a physiology study only, and not one related to treatments, we want to remove any confounders and lessen any chance of drop-out.)
Key exclusion criteria (25 listed)
- Women
- FPG greater than or equal to 100 mg/dl or 2-hr OGTT greater than or equal to 140 mg/dL
- 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
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 |
|---|---|---|
| NabiloneCB agonist | Other | – |
| CP-945,598Cannabinoid Receptor 1 antagonist | Drug | – |
| hyperglycemic clampassesses beta cell response | Other | – |
| euglycemic-hyperinsulinemic clampmeasures insulin sensitivity | Other | – |
| Nabilonecannabinoid receptor agonist | Other | – |
Primary outcome
Changes in insulin sensitivity.
Time frame: CB1R antagonist CP-945,598 will enhance while CR receptor agonist nabilone will suppress first phase insulin response fromB cells in humans
This study will give us a better understanding of the regulators of insulin secretion from B cells and insulin sensitivity in humans and this new understanding is of importance to finding new treatments for type 2 diabetes
1 secondary outcome
Changes in insulin and other hormones and the brain response to picture of food items evidenced by functional MRI of the brain.
Time frame: 90 minutes
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 5 Nov 2026.
- Background: PubMed 11484070Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus. Diabetologia. 2001 Aug;44(8):929-45. doi: 10.1007/s001250100580.
- Background: PubMed 15308461Straub SG, Sharp GW. Hypothesis: one rate-limiting step controls the magnitude of both phases of glucose-stimulated insulin secretion. Am J Physiol Cell Physiol. 2004 Sep;287(3):C565-71. doi: 10.1152/ajpcell.00079.2004.
- Background: PubMed 8224037Elahi D, Muller DC, McAloon-Dyke M, Tobin JD, Andres R. The effect of age on insulin response and glucose utilization during four hyperglycemic plateaus. Exp Gerontol. 1993 Jul-Oct;28(4-5):393-409. doi: 10.1016/0531-5565(93)90066-m.
- Individual participant dataSharing planned: Undecided. The NIA IRP is discussing the plan to make IPD available. A final decision has not been made.
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Screening Protocol
Pain
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 Nabilone, CP-945,598 and hyperglycemic clamp 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 13 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 5 Nov 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. 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?
Changes in insulin sensitivity. (time frame: CB1R antagonist CP-945,598 will enhance while CR receptor agonist nabilone will suppress first phase insulin response fromB cells in humans). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01517100, which also lists 3 linked publications.
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 5 Nov 2026.