Effect of Melatonin on Cardiometabolic Risk- FULL

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

In a 12 week double-blind, placebo-controlled randomized trial, 120 subjects with obesity (BMI≥30 kg/m2) and pre-diabetes (HbA1c, 5.7-6.4%) will be randomly assigned 1:1 to receive either placebo or 2 mg of controlled-release melatonin, taken orally every evening 1 hour before bed. The investigators will assess melatonin's effect on insulin sensitivity by performing a hyperinsulinemic euglycemic glucose clamp and β-islet cell function measured using a hyperglycemic clamp, as a primary endpoint. The investigator will also evaluating melatonin supplementation's effect on mean 24-hour ambulatory blood pressure, nocturnal blood pressure, and potential intermediates including endothelial function using brachial ultrasound, catecholamine production using 24-hour epinephrine and norepinephrine excretion, and renin-angiotensin system activation using measurements of plasma renin activity, angiotensin II, and urine aldosterone excretion. The final endpoint will be to evaluate melatonin supplementation's effect on cellular cytokine and CC family chemokine expression as well as high sensitivity C-reactive protein, IL-6, and TNF-α.

There will be a 24 week cohort phase as an extension of the trial. This will be an open-label prospective study of 50 subjects recruited from the trial who will take 2 mg of controlled-release melatonin nightly for 24 weeks after completion of the 12-week trial. At the end of the cohort-phase (36 weeks after entry in the trial), the investigators will again assess the extended use of melatonin supplementation on 24-hour BP, and glycemic control (HbA1, fasting glucose).

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Brigham and Women's Hospital
• Treatments: Melatonin

Criteria

Inclusion Criteria:

• age ≥18 years

• body mass index (BMI) >30

• HbA1c 5.4-6.4%

• if hypertensive, BP <150/90

Exclusion Criteria:

• Use of a melatonin supplement

• Current use of anticoagulants

• Use of hypoglycemic or antihypertensive meds

• Current or prior history of diabetes mellitus, or random serum glucose ≥ 200 mg/dL

• Major bleeding event in the past 60 days

• Recent (past 2 weeks) or upcoming travel across time zones

• Known obstructive sleep apnea or use of continuous positive airway pressure

• Known heparin allergy

• Hepatic impairment

• Estimated GFR <60 mL/min/1.73m2

• Pregnant

• Job requires rotating night shifts

• Preexisting lung disease requiring oxygen

• Active chronic or acute infection

• Preexisting CVD

• Known melatonin allergy

• Bariatric surgery within the prior 12 months

• Preexisting hemoglobinopathy

• Use of weekly or daily NSAID for chronic pain

• Use of cholesterol lowering medications

• Active or uncontrolled psychotic disorder

• Use of hypnotic medications

• Active or uncontrolled bipolar illness

• Active or uncontrolled depression

• Recent (within the past three months) blood donation or plan to donate blood during study period

• Use of a phosphodiesterase inhibitor

• Active malignancy within the prior 5 years

• Hypertension (>150/90)

• Currently lactating (women)

• History of stroke

• Hematocrit <36 (women) or <41 (men)

• Thrombocytopenia or other bleeding disorders

• Surgery in the past 60 days