Hypertension
Conditions
Keywords
Melatonin, Hypertension, Blood Pressure, Cardiovascular, Sleep, Nighttime, Nocturnal, Catecholamines, Sympathetic Nervous System, Endothelial Function, African American
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.
Interventions
DRUGMelatonin
Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine compound. Subjects will receive 24mg of time release melatonin pills (3 x 8mg) to be taken orally at night for 4 weeks.
DRUGPlacebo
Subjects will receive placebo pills (3 pills) to be taken orally once per night for 4 weeks.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects 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. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Intervention 1 (4 Weeks) | Incarceration | 1 | 0 |
| Intervention 1 (4 Weeks) | Lost to Follow-up | 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
| Characteristic | All Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants |
| Age, Continuous | 48.9 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 36 | 25 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
Mean Nighttime Diastolic Blood Pressure (DBP)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Nighttime Diastolic Blood Pressure (DBP) | 77.2 mmHg | Standard Error 1.7 |
| Placebo | Mean Nighttime Diastolic Blood Pressure (DBP) | 77.6 mmHg | Standard Error 1.7 |
Comparison: The null hypothesis was that there is no interaction between the order of randomization and the primary outcome measures.p-value: 0.0492ANOVA
p-value: 0.95ANOVA
Primary
Mean Nighttime Systolic Blood Pressure (SBP)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Nighttime Systolic Blood Pressure (SBP) | 126.6 mmHg | Standard Error 2.3 |
| Placebo | Mean Nighttime Systolic Blood Pressure (SBP) | 127.9 mmHg | Standard Error 2.3 |
Comparison: The null hypothesis was that there is no interaction between the order of randomization and the primary outcome measures.p-value: 0.0269ANOVA
p-value: 0.84ANOVA
Secondary
Mean Daytime Diastolic Blood Pressure (DBP)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Daytime Diastolic Blood Pressure (DBP) | 85.3 mmHg | Standard Error 1.8 |
| Placebo | Mean Daytime Diastolic Blood Pressure (DBP) | 86.6 mmHg | Standard Error 1.8 |
p-value: 0.12ANOVA
Secondary
Mean Daytime Heart Rate (HR)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Daytime Heart Rate (HR) | 81.6 beats per minute | Standard Error 1.8 |
| Placebo | Mean Daytime Heart Rate (HR) | 83.3 beats per minute | Standard Error 1.8 |
p-value: 0.21ANOVA
Secondary
Mean Daytime Mean Arterial Pressure (MAP)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Daytime Mean Arterial Pressure (MAP) | 101.26 mmHg | Standard Error 1.9 |
| Placebo | Mean Daytime Mean Arterial Pressure (MAP) | 103.5 mmHg | Standard Error 1.9 |
p-value: 0.12ANOVA
Secondary
Mean Daytime Systolic Blood Pressure (SBP)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Daytime Systolic Blood Pressure (SBP) | 134.2 mmHg | Standard Error 2.4 |
| Placebo | Mean Daytime Systolic Blood Pressure (SBP) | 137.3 mmHg | Standard Error 2.4 |
p-value: 0.16ANOVA
Secondary
Mean Nighttime Heart Rate (HR)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Nighttime Heart Rate (HR) | 74.1 beats per minute | Standard Error 1.9 |
| Placebo | Mean Nighttime Heart Rate (HR) | 74.4 beats per minute | Standard Error 1.9 |
p-value: 0.88ANOVA
Secondary
Mean Nighttime Mean Arterial Pressure (MAP)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Mean Nighttime Mean Arterial Pressure (MAP) | 93.9 mmHg | Standard Error 1.8 |
| Placebo | Mean Nighttime Mean Arterial Pressure (MAP) | 94.4 mmHg | Standard Error 1.8 |
p-value: 0.91ANOVA
Secondary
Plasma E-Selectin
E-Selectin is a marker of endothelial function. Levels of e-selectin were measured from stored plasma using enzyme-linked immunosorbent assay (ELISA).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Plasma E-Selectin | 39.5 ng/ml | Standard Error 2.2 |
| Placebo | Plasma E-Selectin | 41.0 ng/ml | Standard Error 2.2 |
p-value: 0.13ANOVA
Secondary
Plasma P-Selectin
P-Selectin is a marker of endothelial function. Levels of p-selectin were measured from stored plasma using enzyme-linked immunosorbent assay (ELISA).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Plasma P-Selectin | 92.2 ng/ml | Standard Error 9.7 |
| Placebo | Plasma P-Selectin | 98.6 ng/ml | Standard Error 9.5 |
p-value: 0.58ANOVA
Secondary
Total Sleep Time
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Total Sleep Time | 415.8 minutes | Standard Error 10.9 |
| Placebo | Total Sleep Time | 413.4 minutes | Standard Error 10.6 |
p-value: 0.39ANOVA
Secondary
Urinary Adrenaline Excretion Rate
The rate of urinary adrenaline excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Urinary Adrenaline Excretion Rate | 1.23 ng/ml/min | Standard Error 0.17 |
| Placebo | Urinary Adrenaline Excretion Rate | 1.76 ng/ml/min | Standard Error 0.17 |
p-value: 0.41Friedman
Secondary
Urinary Dopamine Excretion Rate
The rate of urinary dopamine excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Urinary Dopamine Excretion Rate | 115.5 ng/ml/min | Standard Error 22.3 |
| Placebo | Urinary Dopamine Excretion Rate | 130.8 ng/ml/min | Standard Error 22 |
p-value: 0.06Friedman
Secondary
Urinary Noradrenaline Excretion Rate
The rate of urinary noradrenaline excretion was measured by the Enzyme-Linked Immunosorbent Assay (ELISA) method from urine samples collected overnight.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin | Urinary Noradrenaline Excretion Rate | 11.5 ng/ml/min | Standard Error 2.7 |
| Placebo | Urinary Noradrenaline Excretion Rate | 17 ng/ml/min | Standard Error 2.7 |
p-value: 0.21Friedman