Effect of Melatonin on Cardiometabolic Risk- FULL

NCT02681887 | Unknown Phase 3 DMC FDA Drug

• 1 other identifier: 2015P002524
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Obesity; Prediabetic State

Outcome Measures

Primary Outcomes (2)

• change in insulin sensitivity

  measure insulin sensitivity using hyperinsulinemic clamp

  12 weeks

• change in beta-islet cell function

  measure beta-iset cell function measured using a hyperglycemic clamp

  12 weeks

Secondary Outcomes (12)

• change in 24 hour ambulatory blood pressure

  12 weeks

• change in nocturnal blood pressure

  12 weeks

• change in endothelial dependent vasodilation

  12 weeks

• change in endothelial independent vasodilation

  12 weeks

• change in catecholamine production

  12 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo tablet identical to Circadin by mouth each day before bedtime for 12 weeks

Drug: Placebo

Melatonin

EXPERIMENTAL

Circadin, controlled release melatonin tablet 2mg by mouth each day before bedtime for 12 weeks

Drug: Melatonin

Interventions

Melatonin DRUG

Circadin, controlled release melatonin tablet 2mg by mouth each day before bedtime for 12 weeks

Also known as: Circadian

Melatonin

Placebo DRUG

placebo tablet identical to circadian

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥18 years
• body mass index (BMI) \>30
• HbA1c 5.4-6.4%
• if hypertensive, BP \<150/90

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Obesity; Prediabetic State

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Fatima Adigun, MPH

CONTACT

617-264-3071; fadigun-bello@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 3, 2016
• First Posted: February 15, 2016
• Study Start: September 1, 2016
• Primary Completion: June 1, 2021
• Study Completion: December 1, 2021
• Last Updated: February 22, 2019

Record last verified: 2019-02

Locations

US (1)