Trial Outcomes & Findings for Melatonin and Nighttime Blood Pressure in African Americans--24 mg Study (NCT NCT01114373)

NCT ID: NCT01114373

Last Updated: 2016-02-26

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 are reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 40 participants
• Primary outcome timeframe: 4 weeks
• Results posted on: 2016-02-26

Participant Flow

79 patients came for screening visit. 39 patients were either screen failures or did not want to pursue the study procedures prior to randomization. Ultimately 40 patients were randomized. 4 patients dropped out and 36 completed both arms of the study.

39 patients who came for screening visit, did not make it to the randomization phase either because they didn't meet eligibility criteria or they decided not to pursue with the study procedure.

Participant milestones

Measure	Placebo/Melatonin African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 24mg of placebo at bed time for 4 weeks followed by 24 mg time release melatonin at bed time for 4 weeks.	Melatonin/Placebo African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 24mg daily of time-released melatonin at bed time for 4 weeks, followed by 24 mg of placebo at bed time for 4 week.
Intervention 1 (4 Weeks) STARTED	21	19
Intervention 1 (4 Weeks) COMPLETED	18	19
Intervention 1 (4 Weeks) NOT COMPLETED	3	0
Intervention 2 (4 Weeks) STARTED	18	19
Intervention 2 (4 Weeks) COMPLETED	18	18
Intervention 2 (4 Weeks) NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Placebo/Melatonin African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 24mg of placebo at bed time for 4 weeks followed by 24 mg time release melatonin at bed time for 4 weeks.	Melatonin/Placebo African American subjects with mild to moderate essential hypertension and an elevated nighttime blood pressure \>115 mmHg received 24mg daily of time-released melatonin at bed time for 4 weeks, followed by 24 mg of placebo at bed time for 4 week.
Intervention 1 (4 Weeks) Lost to Follow-up	1	0
Intervention 1 (4 Weeks) Incarceration	1	0
Intervention 1 (4 Weeks) Terminated by PI after protocol violatio	1	0
Intervention 2 (4 Weeks) Lost to Follow-up	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	All Subjects n=36 Participants African American subjects with mild to moderate essential hypertension received melatonin or placebo PO for the first 4 weeks then were switched to receive either placebo or melatonin PO therapy 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
Age, Continuous	48.9 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Nighttime Systolic Blood Pressure (SBP)	126.6 mmHg Standard Error 2.3	127.9 mmHg Standard Error 2.3

PRIMARY outcome

Timeframe: 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.

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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Nighttime Diastolic Blood Pressure (DBP)	77.2 mmHg Standard Error 1.7	77.6 mmHg Standard Error 1.7

SECONDARY outcome

Timeframe: 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.

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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Nighttime Mean Arterial Pressure (MAP)	93.9 mmHg Standard Error 1.8	94.4 mmHg Standard Error 1.8

SECONDARY outcome

Timeframe: 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.

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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Nighttime Heart Rate (HR)	74.1 beats per minute Standard Error 1.9	74.4 beats per minute Standard Error 1.9

SECONDARY outcome

Timeframe: 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.

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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Daytime Systolic Blood Pressure (SBP)	134.2 mmHg Standard Error 2.4	137.3 mmHg Standard Error 2.4

SECONDARY outcome

Timeframe: 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.

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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Daytime Diastolic Blood Pressure (DBP)	85.3 mmHg Standard Error 1.8	86.6 mmHg Standard Error 1.8

SECONDARY outcome

Timeframe: 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 are 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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Daytime Mean Arterial Pressure (MAP)	101.26 mmHg Standard Error 1.9	103.5 mmHg Standard Error 1.9

SECONDARY outcome

Timeframe: 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 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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Mean Daytime Heart Rate (HR)	81.6 beats per minute Standard Error 1.8	83.3 beats per minute Standard Error 1.8

SECONDARY outcome

Timeframe: 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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Urinary Dopamine Excretion Rate	115.5 ng/ml/min Standard Error 22.3	130.8 ng/ml/min Standard Error 22

SECONDARY outcome

Timeframe: 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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Urinary Noradrenaline Excretion Rate	11.5 ng/ml/min Standard Error 2.7	17 ng/ml/min Standard Error 2.7

SECONDARY outcome

Timeframe: 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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Urinary Adrenaline Excretion Rate	1.23 ng/ml/min Standard Error 0.17	1.76 ng/ml/min Standard Error 0.17

SECONDARY outcome

Timeframe: 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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Plasma E-Selectin	39.5 ng/ml Standard Error 2.2	41.0 ng/ml Standard Error 2.2

SECONDARY outcome

Timeframe: 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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Plasma P-Selectin	92.2 ng/ml Standard Error 9.7	98.6 ng/ml Standard Error 9.5

SECONDARY outcome

Timeframe: 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.

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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin)
Total Sleep Time	415.8 minutes Standard Error 10.9	413.4 minutes Standard Error 10.6

Adverse Events

Melatonin

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 25 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 24mg 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 4 weeks (either before or after 4 weeks of exposure to 24mg daily dose of time release melatonin).
General disorders Fatigue	41.7% 15/36 • 8 weeks 36 subjects completed the study.	33.3% 12/36 • 8 weeks 36 subjects completed the study.
General disorders Daytime drowsiness	36.1% 13/36 • 8 weeks 36 subjects completed the study.	30.6% 11/36 • 8 weeks 36 subjects completed the study.
General disorders Early Morning Wakening	38.9% 14/36 • 8 weeks 36 subjects completed the study.	27.8% 10/36 • 8 weeks 36 subjects completed the study.
General disorders Dizziness	11.1% 4/36 • 8 weeks 36 subjects completed the study.	8.3% 3/36 • 8 weeks 36 subjects completed the study.
Gastrointestinal disorders Nausea	11.1% 4/36 • 8 weeks 36 subjects completed the study.	8.3% 3/36 • 8 weeks 36 subjects completed the study.
General disorders Weakness	11.1% 4/36 • 8 weeks 36 subjects completed the study.	8.3% 3/36 • 8 weeks 36 subjects completed the study.
Eye disorders Blurred vision	11.1% 4/36 • 8 weeks 36 subjects completed the study.	11.1% 4/36 • 8 weeks 36 subjects completed the study.

Additional Information

Frederic Rahbari-Oskoui, Associate Professor of Medicine

Emory University

Phone: 404-727-3425

Email: frahbar@emory.edu

Results disclosure agreements

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