Melatonin and Nighttime Blood Pressure in African Americans--24 mg Study

Phase 2

Completed

Conditions: Hypertension

Interventions: Drug: Melatonin
Drug: Placebo

Registration Number: NCT01114373

Lead Sponsor: Emory University

Brief Summary: The purpose of this study is to test the effect of oral melatonin supplementation (24 mg per night for 4 weeks) on nighttime blood pressure in African Americans with a history of elevated nighttime blood pressure.

Detailed Description: The main outcome of interest is the mean nighttime blood pressure. The investigator is also trying to see the mechanism of action of melatonin on blood pressure by analyzing data from sleep studies to see if melatonin lowers blood pressure by providing a better quality of sleep or is that independent of the quality of sleep.

The investigator is also looking into the effect of melatonin on sympathetic nervous system by measuring urinary catecholamines.

Finally, the investigator is looking into changes in vascular biology markers P-selectin and e-selectin) on Melatonin.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

Inclusion Criteria

Males or females ages 18 to 64
Prior history of elevated nighttime blood pressure (BP) ((systolic blood pressure (SBP) > 115mmHg))
Taking no more than 2 antihypertensive medications
African American (self-defined by the participant)

Exclusion Criteria

Secondary forms of hypertension
Presence of other diseases requiring treatment with BP lowering medication
Known cardiovascular disease (including history of angina pectoris, heart failure, presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or history of cerebrovascular disease, including stroke and transient ischemic attacks)
Diabetes mellitus (Type 1 or 2)
Cancer/malignancy other than nonmelanoma skin cancer
Primary renal disease
Serum creatinine > 1.5 mg/dL in men or > 1.4 mg/dL in women
Severe anemia
Liver enzymes > 2.5 times upper limits of normal
Hepatitis B, Hepatitis C, or HIV positive as assessed by questionnaire
Current treatment with or regular use of calcium channel blocking agents, cyclooxygenase-2 inhibitors (COX2-I), oral contraceptives, estrogen, sildenafil, vardenafil, tadalafil, antidepressants, corticosteroids, or warfarin
Current use of melatonin or any sleep aids containing melatonin
Regular consumption (1 or more times per week) of: Vitamin methyl B12, St. Johns Wort, feverfew, black and white mustard seeds, wolf berry seed
Severe Sleep apnea
Night work
Women who are pregnant, breast feeding, attempting conception, or planning to attempt conception over the next 6 months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects with mild to moderate essential hypertension will be given placebo for 4 weeks either before or after exposure to 4 weeks of 24mg daily dose of time release melatonin with no washout period.
Melatonin	Placebo	Subjects with mild to moderate essential hypertension will be given 24mg time release melatonin for 4 weeks either before or after exposure to 4 week of placebo with no washout period.
Melatonin	Melatonin	Subjects with mild to moderate essential hypertension will be given 24mg time release melatonin for 4 weeks either before or after exposure to 4 week of placebo with no washout period.
Placebo	Melatonin	Subjects with mild to moderate essential hypertension will be given placebo for 4 weeks either before or after exposure to 4 weeks of 24mg daily dose of time release melatonin with no washout period.

Primary Outcome Measures

Name	Time	Method
Mean Nighttime Systolic Blood Pressure (SBP)	4 weeks	The nighttime systolic blood pressure (SBP) was recorded using an ambulatory blood pressure (ABP) monitor. The measurements occurring from the onset of self-reported sleep to the end of self-reported sleep were recorded. Means of multiple measurements are reported.
Mean Nighttime Diastolic Blood Pressure (DBP)	4 weeks	The nighttime diastolic blood pressure (DBP) was recorded using an ambulatory blood pressure (ABP) monitor. The measurements occurring from the onset of self-reported sleep to the end of self-reported sleep were recorded. Means of multiple measurements are reported.

Secondary Outcome Measures

Name	Time	Method
Mean Daytime Heart Rate (HR)	4 weeks	Daytime heart rate is the number of pulsations of the heart per unit of time. It is measured in beats per minute (bpm). The ambulatory blood pressure monitor was used to calculate the heart rate. Means of multiple measurements are reported.
Urinary Dopamine Excretion Rate	4 weeks	The rate of urinary dopamine excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.
Urinary Noradrenaline Excretion Rate	4 weeks	The rate of urinary noradrenaline excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.
Urinary Adrenaline Excretion Rate	4 weeks	The rate of urinary adrenaline excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.
Plasma E-Selectin	4 weeks	E-Selectin is a marker of endothelial function. Levels of e-selectin were measured from stored plasma using enzyme-linked immunosorbent assay (ELISA).
Plasma P-Selectin	4 weeks	P-Selectin is a marker of endothelial function. Levels of p-selectin were measured from stored plasma using enzyme-linked immunosorbent assay (ELISA).
Total Sleep Time	4 weeks	The total sleep time will be measured by polysomnography (PSG) using an Embla polysomnograph. The nocturnal total sleep time (TST) or the the total number of minutes in any stage of sleep during the major nocturnal sleep period was measured by PSG.
Mean Nighttime Mean Arterial Pressure (MAP)	4 weeks	Nighttime mean arterial pressure (MAP) is the average blood pressure in the subject's arteries during one cardiac cycle (one complete heartbeat) at night. It is calculated using the formula, MAP = 1/3(SBP-DBP)+DBP; where SBP is the systolic blood pressure and DBP is the diastolic blood pressure. Means of multiple measurements are reported.
Mean Nighttime Heart Rate (HR)	4 weeks	Nighttime heart rate is the number of pulsations of the heart per unit of time. It is measured in beats per minute (bpm). The ambulatory blood pressure monitor was used to calculate the heart rate. Means of multiple measurements are reported.
Mean Daytime Systolic Blood Pressure (SBP)	4 weeks	The daytime systolic blood pressure was calculated as the average systolic blood pressure during daytime period based on 24hour ambulatory blood pressure monitoring. Means of multiple measurements are reported.
Mean Daytime Diastolic Blood Pressure (DBP)	4 weeks	The daytime diastolic blood pressure was calculated as the average diastolic blood pressure during the daytime period based on 24 hour ambulatory blood pressure monitoring. Means of multiple measurements are reported.
Mean Daytime Mean Arterial Pressure (MAP)	4 weeks	Daytime mean arterial pressure (MAP) is the average blood pressure in the subject's arteries during one cardiac cycle (one complete heartbeat) during the day. It is calculated using the formula, MAP = 1/3(SBP-DBP)+DBP; where SBP is the systolic blood pressure and DBP is the diastolic blood pressure. Means of multiple measurements are reported.