Melatonin and Nighttime Blood Pressure in African Americans-8 mg Study

Phase 2

Completed

Conditions: Hypertension

Interventions: Drug: Melatonin
Drug: Placebo

Registration Number: NCT01114360

Lead Sponsor: Emory University

Brief Summary: This purpose of this study is to test the effect of oral melatonin supplementation (8 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: 37

Inclusion Criteria

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

Exclusion Criteria

Secondary forms of hypertension
Presence of other diseases requiring treatment with BP lowering medications
Known cardiovascular disease (including history of angina pectoris, heart failure, presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or 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 > 1.4mg/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 or COX2-inhibitors, 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 any of the following 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	African-American subjects with mild to moderate essential hypertension will be given placebo for 4 weeks (either before or after exposure to melatonin)
Melatonin	Placebo	African-American subjects with mild to moderate essential hypertension will be given 8mg time release melatonin for 4 weeks. (either before or after placebo exposure).
Melatonin	Melatonin	African-American subjects with mild to moderate essential hypertension will be given 8mg time release melatonin for 4 weeks. (either before or after placebo exposure).
Placebo	Melatonin	African-American subjects with mild to moderate essential hypertension will be given placebo for 4 weeks (either before or after exposure to melatonin)

Primary Outcome Measures

Name	Time	Method
Mean Nighttime Diastolic Blood Pressure (DBP)	At the end of 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 were reported
Mean Nighttime Systolic Blood Pressure (SBP)	At the end of 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 were reported.

Secondary Outcome Measures

Name	Time	Method
Mean Daytime Diastolic Blood Pressure (DBP)	At the end of 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 were reported
Mean Daytime Mean Arterial Pressure (MAP)	At the end of 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 were reported.
Plasma P-Selectin	At the end of 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).
Mean Daytime Systolic Blood Pressure (SBP)	At the end of 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 were reported
Mean Nighttime Mean Arterial Pressure (MAP)	At the end of 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 were reported
Mean Nighttime Heart Rate (HR)	At the end of 4 weeks	Nighttime heart rate is number of pulsations of the heart per unit of time during nighttime sleep. It is measured in beats per minute (bpm). Ambulatory blood pressure monitoring was used to calculate the heart rate. Means of multiple measurements were reported
Urinary Dopamine Excretion Rate	At the end of 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	At the end of 4 weeks	The rate of urinary noradrenaline excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.
Mean Daytime Heart Rate (HR)	At the end of 4 weeks	Daytime heart rate is the number of the pulsations of the heart per unit of time during the day. It is measured in beats per minute (bpm). Ambulatory blood pressure monitoring was used to calculate the heart rate. Means of multiple measurements were reported
Total Sleep Time	At the end of 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.
Nocturnal Dipping of Blood Pressure	At the end of 4 weeks	Nocturnal dipping is the mean nighttime to mean daytime systolic and diastolic blood pressure ratios, or the percentage drop in nocturnal SBP compared to day time SBP. Night was defined as 10:00 PM through 5:59 AM. This ratio is calculated by the ambulatory blood pressure readings.
Percentage of Participants With Melatonin-related Side Effect.	After 4 weeks of treatment
Urinary Adrenaline Excretion Rate	At the end of 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	At the end of 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).