THC Effects on Glucose in Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT05322213
• Recruitment Status: Not yet recruiting
• First Posted: April 11, 2022
• Last Update Posted: January 25, 2023
• Sponsor: University of California, San Diego
• Collaborator: Center for Medicinal Cannabis Research
• Information provided by (Responsible Party): Jeremy Pettus, MD, University of California, San Diego

Tracking Information

• First Submitted Date: March 30, 2022
• First Posted Date: April 11, 2022
• Last Update Posted Date: January 25, 2023
• Estimated Study Start Date: May 1, 2023
• Estimated Primary Completion Date: April 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 8, 2022)

• Change in Glucose Uptake [ Time Frame: 6 weeks ]
  The change in glucose uptake from placebo treatment to THC treatment as measure by the hyperinsulinemic/euglycemic clamp.
• Change in Vascular Endothelial Function [ Time Frame: 6 weeks ]
  The change in vascular endothelial function from placebo treatment to THC treatment as measured by flow mediated dilation (brachial artery diameter).
• Change in Vascular Endothelial Function [ Time Frame: 6 weeks ]
  The change in vascular endothelial function from placebo treatment to THC treatment as measured by reactive hyperemia-peripheral arterial tonometry (reactive hyperemia index).

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: THC Effects on Glucose in Type 2 Diabetes
• Official Title: The Effects of THC on Glucose Metabolism and Endothelial Function in Subjects With Type 2 Diabetes
• Brief Summary: This study will examine the effects THC has on Glucose Metabolism and Endothelial Functioning in participants with Type 2 Diabetes. The participants will complete blood tests and tests to measure energy expenditure, CVD risks, and glucose metabolism. These tests will be performed prior to start of treatment and again after 2-weeks of treatment with the THC or placebo.

Detailed Description

A single-center, double-blind, placebo-controlled, cross-over study designed to evaluate the effects of THC on glucose metabolism and endothelial functioning in individuals with type 2 diabetes. To accomplish the specific AIMS proposed, a single clinical trial will be conducted in which a maximum of 30 subjects with T2D, who are otherwise healthy, will be treated with THC and matching placebo in a cross-over study design. Each treatment period will be 2 weeks in duration with metabolic and endothelial assessments done post-therapy. Subjects will be randomized on a 1:1 basis to either receive either THC or placebo for the first 2 weeks of therapy. Then following a 4-week washout, they will receive the opposite investigational product for the second 2 weeks of therapy. Subjects will remain on their standard treatment for T2D throughout the entire course of the study. There will be a total of 10 study visits and subjects will be enrolled for approximately 16 weeks.

1. Screening - Complete consenting process, complete medical history and physical exam, review of current medications, collect height/weight, vital signs, ECG and fasting laboratory (blood and urine) tests.
2. Visit 2 - Treatment Session 1 Start - Collect weight, vital signs and fasting laboratory tests. Receive investigational product and training on its use.
3. Visit 3 - Monitory investigational product compliance and adjust dosing.
4. Visit 4 - Complete endothelial function tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety.
5. Visit 5 - Complete a 2-Step Hyperinsulinemic/Euglycemic clamp and Indirect Calorimetry. Begin 4-week washout.
6. Visit 6 - Treatment Session 2 Start - Collect weight, vital signs and receive investigational product and training on its use.
7. Visit 7 - Monitory investigational product compliance and adjust dosing.
8. Visit 8 - Complete endothelial function tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety.
9. Visit 9 - Complete a 2-Step Hyperinsulinemic/Euglycemic clamp and Indirect Calorimetry. Discontinue use of investigational product.
10. Safety Follow-up - Collect weight, vital signs, ECG and fasting laboratory tests. Receive investigational product and training on its use.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Single-Center, double-blind, placebo-controlled, crossover study.

Masking: Double (Participant, Investigator)
Masking Description:

Double-blind

Primary Purpose: Basic Science

• Condition: Type 2 Diabetes

Intervention

• Drug: THC
  2-Week, once daily, flexible dose, inhaled THC
  Other Name: Cannabis
• Drug: Placebo
  2-Week, once daily, flexible dose, inhaled placebo

Study Arms

• Active Comparator: Active THC
  Daily, inhaled, flexible dose of cannabis product with THC.
  Interventions:

  • Drug: THC
  • Drug: Placebo
• Placebo Comparator: Placebo Cannabis
  Daily, inhaled, flexible dose of cannabis product without THC.
  Interventions:

  • Drug: THC
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: April 8, 2022): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 30, 2027
• Estimated Primary Completion Date: April 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Males and Females 21-70 years old at the time of screening.
• Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study.
• Male subjects must be willing to use clinically acceptable method of contraception during the entire study.
• Have a clinical diagnosis of Type 2 Diabetes on a stable medication regimen for at least 3 months.
• BMI > 25 kg/m2).
• HbA1c < 10%).
• Negative urine toxicology result at screening visit.
• Able to provide written informed consent approved by an Institutional Review Board (IRB).

Exclusion Criteria:

• History or presence of any clinically significant illness, as detected by history, physical examination, and/or laboratory tests, that might put the participant at increased risk of adverse events (e.g., history of psychotic disorder, clinically significant mood and/or anxiety disorder, liver, or renal disease).
• No prior history of myocardial infarction, stroke or heart failure.
• Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion.
• Hemoglobin < 9g/dL.
• Liver enzymes ≥ 2 times upper normal limit and/or clinical signs/symptoms consistent with liver disease, including but not limited to nausea, vomiting, jaundice, itching, abdominal pain, or edema.
• History of clinically significant adverse events associated with cannabis intoxication (e.g., severe anxiety and panic, paranoia and psychosis, sustained tachycardia, or severe hypotension).
• History of seizures, head trauma, or other history of CNS insult that could predispose the participant to seizures.
• Use of any THC containing products within 30 days prior to the screening visit.
• Current use of tobacco products.
• Individuals who are pregnant or lactating/breastfeeding.
• Current use of insulin to treat Type 2 Diabetes.
• Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits.
• Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Todd May, MS; 858-246-2169; tmay@health.ucsd.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05322213
• Other Study ID Numbers: 802153
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jeremy Pettus, MD, University of California, San Diego
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Diego
• Original Study Sponsor: Same as current
• Collaborators: Center for Medicinal Cannabis Research
• Investigators: Not Provided
• PRS Account: University of California, San Diego
• Verification Date: January 2023