THC Effects on Glucose in Type 2 Diabetes

Study Overview
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Brief Summary
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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
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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. 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. Visit 2 - Treatment Session 1 Start - Collect weight, vital signs and fasting laboratory tests. Receive investigational product and training on its use. Visit 3 - Monitory investigational product compliance and adjust dosing. Visit 4 - Complete endothelial function tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety. Visit 5 - Complete a 2-Step Hyperinsulinemic/Euglycemic clamp and Indirect Calorimetry. Begin 4-week washout. Visit 6 - Treatment Session 2 Start - Collect weight, vital signs and receive investigational product and training on its use. Visit 7 - Monitory investigational product compliance and adjust dosing. Visit 8 - Complete endothelial function tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety. Visit 9 - Complete a 2-Step Hyperinsulinemic/Euglycemic clamp and Indirect Calorimetry. Discontinue use of investigational product. Safety Follow-up - Collect weight, vital signs, ECG and fasting laboratory tests. Receive investigational product and training on its use.

Official Title
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The Effects of THC on Glucose Metabolism and Endothelial Function in Subjects With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: THC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-Center, double-blind, placebo-controlled, crossover study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active THC<br>Daily, inhaled, flexible dose of cannabis product with THC. | Drug: THC<br>* 2-Week, once daily, flexible dose, inhaled THC<br>* Other names: Cannabis;Drug: Placebo<br>* 2-Week, once daily, flexible dose, inhaled placebo<br>|
| Placebo Comparator: Placebo Cannabis<br>Daily, inhaled, flexible dose of cannabis product without THC. | Drug: THC<br>* 2-Week, once daily, flexible dose, inhaled THC<br>* Other names: Cannabis;Drug: Placebo<br>* 2-Week, once daily, flexible dose, inhaled placebo<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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THC