The Role of Endocannabinoids in Insulin Production and Action

NCT01517100 | Completed Phase 1 FDA Drug

• 2 other identifiers: 99991201812-AG-N018
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Healthy Volunteers

Keywords

Glucose; Insulin Secretion; Insulin Action; Endocannabinoids; Insulin; Metabolism

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  90 minutes

Interventions

Nabilone OTHER

CB agonist

hyperglycemic clamp OTHER

assesses beta cell response

euglycemic-hyperinsulinemic clamp OTHER

measures insulin sensitivity

CP-945,598 DRUG

Cannabinoid Receptor 1 antagonist

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• National Institute on Aging (NIA): lead

Study Sites (1)

National Institute of Aging, Clinical Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Publications (3)

• 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.

  PMID: 11484070 BACKGROUND

• Straub 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.

  PMID: 15308461 BACKGROUND

• Elahi 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.

  PMID: 8224037 BACKGROUND

MeSH Terms

Conditions

Insulin Resistance

Interventions

nabilone

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Chee W Chia, M.D.

  National Institute on Aging (NIA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: January 25, 2012
• Study Start: January 5, 2012
• Primary Completion: October 6, 2014
• Study Completion: October 6, 2014
• Last Updated: March 31, 2026

Record last verified: 2026-03-11

Locations

US (1)