Effects of Melatonin to Reduce Nocturnal Hypertension in Patients With Neurogenic Orthostatic Hypotension

NCT02963181 | Terminated Early Phase 1

• 1 other identifier: 010788
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Neurogenic Orthostatic Hypotension (NOH) is clinically defined as a consistent drop in systolic blood pressure (SBP) ≥30mmHg upon standing from a seated or lying position. However, 50% of NOH patients also have associated supine hypertension. It has been proposed that supine hypertension is the result of intact post-ganglionic sympathetic nerves and therefore due to residual sympathetic tone. Furthermore, research investigating the effects of melatonin shows blood pressure implication of this naturally secreted hormone. Specifically, melatonin has been investigated as a non-traditional anti-hypertensive agent for patients with essential and nocturnal hypertension. Central and peripheral mechanisms have been proposed to help explain how melatonin reduces blood pressures. Therefore, we aim to identify NOH patients as having either intact or denervated post-ganglionic sympathetic nerves, monitor the correlation to supine hypertension and subsequently investigate the effects of melatonin on blood pressure in these patients.

Conditions

Hypotension, Orthostatic; Hypertension; Autonomic Nervous System Diseases

Keywords

Melatonin; Yohimbine; Anti-hypertensive agents

Outcome Measures

Primary Outcomes (3)

• Investigation into the integrity of post-ganglionic sympathetic nerves in idiopathic NOH

  Markers of post-ganglionic sympathetic function will be examined (i.e. sympathetic blood markers, heart rate, blood pressure, sympathetic nerve activity, etc.)

  Sympathetic markers will be assessed during and immediately following the test. A comparison between healthy participants and NOH patients will be ongoing throughout recruitment and upon completion of study recruitment

• Effects of melatonin on supine hypertension in persons with neurogenic orthostatic hypotension

  Supine systolic blood pressure

  4 weeks

• Effects of melatonin on supine hypertension in patients with neurogenic orthostatic hypotension

  Change in postural (supine-standing) systolic blood pressure

  4 weeks

Secondary Outcomes (6)

• Serum markers of sympathetic activation

  Before and during stimulation of sympathetic nervous system

• Carotid artery diameter

  During stimulation of sympathetic nervous system

• Sympathetic nerve activation using microneurography

  During stimulation of sympathetic nervous system

• Orthostatic symptoms based on standard autonomic symptom questionnaires

  30 minutes before testing

• Sleep quality assessment using Epworth Sleepiness Scale

  Assessed at pre- and post- melatonin treatment; week 1 and week 5 of melatonin intervention timeframe

Study Arms (2)

Effects of Yohimbine

EXPERIMENTAL

Investigation into the integrity of post-ganglionic sympathetic nerves in patients with idiopathic neurogenic orthostatic hypotension

Drug: Yohimbine

Effects of melatonin on blood pressure

EXPERIMENTAL

Investigation into the effects of melatonin at two separate dosages (2 and 5mg) on nocturnal blood pressure in NOH patients with intact versus denervated post-ganglionic sympathetic nerves

Drug: Melatonin

Interventions

Yohimbine DRUG

Oral Yohimbine will be used to identify the integrity of post-ganglionic sympathetic nerves in patients with NOH

Also known as: DIN:01901885

Effects of Yohimbine

Melatonin DRUG

Monitor the effects of melatonin on supine hypertension in NOH patients with intact and denervated post-ganglionic nerves. Identify the mechanistic pathway of melatonin in blood pressure regulation

Also known as: melatonin timed release; 2 or 5 mg

Effects of melatonin on blood pressure

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Control population: Healthy males or females between the ages of 18-80.
• Patient population: Males or females who have been previously diagnosed with Neurogenic Orthostatic Hypotension.

You may not qualify if:

• Patient population:
• Medical therapies or medications which could interfere with testing of autonomic function.
• Clinically significant heart disease.
• Presence of unrelated nerve damage in the peripheral nervous system.
• Pregnant or breast feeding females.
• The presence of failure of other organ systems or systemic illness that can affect autonomic function or your ability to cooperate. These include dementia, heart failure, kidney or liver disease, severe anemia, alcoholism, any new and abnormal cell growth identified as malignant, hypothyroidism, surgical procedures where the nerves of the sympathetic nervous system have been cut, or cerebrovascular disease.
• \. All the above PLUS No lying/night time hypertension as determined by 24-hour blood pressure monitoring
• Presence of ANY autonomic dysfunction
• Medical therapies or medications which could interfere with testing of autonomic function.
• Clinically significant heart disease.
• Presence of ANY nerve damage in the peripheral nervous system.
• Pregnant or breast feeding females.
• The presence of failure of other organ systems or systemic illness that can affect autonomic function or your ability to cooperate. These include dementia, heart failure, kidney or liver disease, severe anemia, alcoholism, any new and abnormal cell growth identified as malignant, hypothyroidism, surgical procedures where the nerves of the sympathetic nervous system have been cut, or cerebrovascular disease.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

University Hospital

London, Ontario, N6A5A5, Canada

Location

Related Publications (29)

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MeSH Terms

Conditions

Hypotension, Orthostatic; Hypertension; Autonomic Nervous System Diseases

Interventions

Yohimbine; Melatonin

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Tryptamines; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2016
• First Posted: November 15, 2016
• Study Start: March 1, 2018
• Primary Completion: May 28, 2019
• Study Completion: May 28, 2019
• Last Updated: June 12, 2019

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)