Trial Outcomes & Findings for Melatonin and Nighttime Blood Pressure in African Americans-8 mg Study (NCT NCT01114360)

NCT ID: NCT01114360

Last Updated: 2015-12-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: At the end of 4 weeks
• Results posted on: 2015-12-18

Participant Flow

80 patients were screened. 43 patients stopped study participation prior to randomization either due to screen failure or because the decided not to pursue the study procedures. 37 patients were randomized. There was 1 dropout, and 36 patients completed both arms of the study.

After signing the ICF and going through screening procedures, 43 patients stopped study participation prior to randomization either due to screen failure or because the decided not to pursue the study procedures.

Participant milestones

Measure	Placebo/Melatonin African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg of placebo for 4 weeks first, followed by 8 mg of time-released melatonin for 4 weeks.	Melatonin/Placebo African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8 mg of time released melatonin at bed time for 4 weeks, followed by 8 mg of placebo at bedtime for an additional 4 weeks.
Intervention 1 (4 Weeks) STARTED	18	19
Intervention 1 (4 Weeks) COMPLETED	18	18
Intervention 1 (4 Weeks) NOT COMPLETED	0	1
Intervention 2 (4 Weeks) STARTED	18	18
Intervention 2 (4 Weeks) COMPLETED	18	18
Intervention 2 (4 Weeks) NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Placebo/Melatonin African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg of placebo for 4 weeks first, followed by 8 mg of time-released melatonin for 4 weeks.	Melatonin/Placebo African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8 mg of time released melatonin at bed time for 4 weeks, followed by 8 mg of placebo at bedtime for an additional 4 weeks.
Intervention 1 (4 Weeks) Physician Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	All Participants n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg of time release melatonin or placebo for the first 4 weeks and were then switched to receive either placebo or 8mg of time release melatonin for an additional 4 weeks without any wash out period in between.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Nighttime Systolic Blood Pressure (SBP)	126.6 mmHg Standard Error 2.4	125.3 mmHg Standard Error 2.5

PRIMARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Nighttime Diastolic Blood Pressure (DBP)	76 mmHg Standard Error 1.7	76.2 mmHg Standard Error 1.8

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Nighttime Mean Arterial Pressure (MAP)	92.9 mmHg Standard Error 1.9	92.6 mmHg Standard Error 2.0

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Nighttime Heart Rate (HR)	75.4 beats per minute Standard Error 2	76.2 beats per minute Standard Error 2.1

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Daytime Systolic Blood Pressure (SBP)	135.13 mmHg Standard Error 2.2	133.9 mmHg Standard Error 2.2

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Daytime Diastolic Blood Pressure (DBP)	85.7 mmHg Standard Error 1.6	86.2 mmHg Standard Error 1.7

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 40 subjects enrolled the study. 4 subjects did not complete the study. 36 subjects completed the study in a crossover design, being their own controls.

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.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Daytime Mean Arterial Pressure (MAP)	102.2 mmHg Standard Error 1.7	102.1 mmHg Standard Error 1.8

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Mean Daytime Heart Rate (HR)	81 beats per minute Standard Error 1.9	84.6 beats per minute Standard Error 1.9

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

The rate of urinary dopamine excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Urinary Dopamine Excretion Rate	140.9 ng/ml/min Standard Error 13.2	137.8 ng/ml/min Standard Error 13.0

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

The rate of urinary noradrenaline excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Urinary Noradrenaline Excretion Rate	17.5 ng/ml/min Standard Error 3.0	19.0 ng/ml/min Standard Error 3.0

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 40 patients were enrolled in the study. 4 subjects did not complete the study. 36 patients completed the study and were their own controls.

The rate of urinary adrenaline excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Urinary Adrenaline Excretion Rate	2.75 ng/ml/min Standard Error 0.6	2.02 ng/ml/min Standard Error 0.6

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

E-Selectin is a marker of endothelial function. Levels of e-selectin were measured from stored plasma using enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Plasma E-Selectin	38.6 ng/ml Standard Error 2.1	38.9 ng/ml Standard Error 2.1

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

P-Selectin is a marker of endothelial function. Levels of p-selectin were measured from stored plasma using enzyme-linked immunosorbent assay (ELISA).

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Plasma P-Selectin	97.02 ng/ml Standard Error 7.6	82.7 ng/ml Standard Error 7.6

SECONDARY outcome

Timeframe: At the end of 4 weeks

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

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.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Total Sleep Time	399.8 minutes Standard Error 11.0	412.2 minutes Standard Error 11.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Nocturnal Dipping of Blood Pressure	5.6 percentage ratio in night/day SBP Standard Error 1.23	6.14 percentage ratio in night/day SBP Standard Error 1.30

SECONDARY outcome

Timeframe: After 4 weeks of treatment

Population: 37 subjects enrolled the study. 1 subject did not complete the two arms of the study. 36 subjects completed the study in a crossover design, being their own controls.

Outcome measures

Measure	Melatonin n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 Participants African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
Percentage of Participants With Melatonin-related Side Effect.	47.2 percentage of total number of patients	50 percentage of total number of patients

Adverse Events

Melatonin

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Melatonin n=36 participants at risk African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 8mg time release melatonin for 4 weeks (either before or after 4 weeks of exposure to placebo).	Placebo n=36 participants at risk African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received placebo for four weeks (either before or after 4 weeks of exposure to 8 mg daily dose of time release melatonin).
General disorders Fatigue	30.6% 11/36 • 4 weeks on each arm.	36.1% 13/36 • 4 weeks on each arm.
General disorders Daytime drowsiness	30.6% 11/36 • 4 weeks on each arm.	33.3% 12/36 • 4 weeks on each arm.
General disorders Early Morning Wakening	33.3% 12/36 • 4 weeks on each arm.	30.6% 11/36 • 4 weeks on each arm.
General disorders Dizziness	8.3% 3/36 • 4 weeks on each arm.	16.7% 6/36 • 4 weeks on each arm.
Gastrointestinal disorders Nausea	8.3% 3/36 • 4 weeks on each arm.	13.9% 5/36 • 4 weeks on each arm.
General disorders Weakness	5.6% 2/36 • 4 weeks on each arm.	13.9% 5/36 • 4 weeks on each arm.
Eye disorders Blurred vision	8.3% 3/36 • 4 weeks on each arm.	11.1% 4/36 • 4 weeks on each arm.
Cardiac disorders Heart palpitations	5.6% 2/36 • 4 weeks on each arm.	5.6% 2/36 • 4 weeks on each arm.

Additional Information

Frederic Rahbari-Oskoui, Associate Professor of Medicine

Emory University

Phone: 404-727-2590

Email: frahbar@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place