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

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ClinicalTrials.gov Identifier: NCT02963181
Recruitment Status : Recruiting
First Posted : November 15, 2016
Last Update Posted : March 9, 2018
Sponsor:
Information provided by (Responsible Party):
Lawson Health Research Institute

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.

Condition or disease Intervention/treatment Phase
Hypotension, Orthostatic Hypertension Autonomic Nervous System Diseases Drug: Yohimbine Drug: Melatonin Early Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Identifying the Pathophysiology of Neurogenic Orthostatic Hypotension and the Effects of Melatonin on Reducing Supine Hypertension in Peripherally Intact Versus Denervated Post-ganglionic Sympathetic Nerves
Actual Study Start Date : March 1, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Experimental: Effects of Yohimbine
Investigation into the integrity of post-ganglionic sympathetic nerves in patients with idiopathic neurogenic orthostatic hypotension
Drug: Yohimbine
Oral Yohimbine will be used to identify the integrity of post-ganglionic sympathetic nerves in patients with NOH
Other Name: DIN:01901885

Experimental: Effects of melatonin on blood pressure
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

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

Other Name: melatonin timed release; 2 or 5 mg




Primary Outcome Measures :
  1. Investigation into the integrity of post-ganglionic sympathetic nerves in idiopathic NOH [ Time Frame: 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 ]
    Markers of post-ganglionic sympathetic function will be examined (i.e. sympathetic blood markers, heart rate, blood pressure, sympathetic nerve activity, etc.)

  2. Effects of melatonin on supine hypertension in persons with neurogenic orthostatic hypotension [ Time Frame: 4 weeks ]
    Supine systolic blood pressure

  3. Effects of melatonin on supine hypertension in patients with neurogenic orthostatic hypotension [ Time Frame: 4 weeks ]
    Change in postural (supine-standing) systolic blood pressure


Secondary Outcome Measures :
  1. Serum markers of sympathetic activation [ Time Frame: Before and during stimulation of sympathetic nervous system ]
  2. Carotid artery diameter [ Time Frame: During stimulation of sympathetic nervous system ]
  3. Sympathetic nerve activation using microneurography [ Time Frame: During stimulation of sympathetic nervous system ]
  4. Orthostatic symptoms based on standard autonomic symptom questionnaires [ Time Frame: 30 minutes before testing ]
  5. Sleep quality assessment using Epworth Sleepiness Scale [ Time Frame: Assessed at pre- and post- melatonin treatment; week 1 and week 5 of melatonin intervention timeframe ]
  6. Urine and Saliva melatonin levels [ Time Frame: Assessed at pre- and post- melatonin treatment; week 1 and week 5 of melatonin intervention timeframe ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

Patient population:

  1. Medical therapies or medications which could interfere with testing of autonomic function.
  2. Clinically significant heart disease.
  3. Presence of unrelated nerve damage in the peripheral nervous system.
  4. Pregnant or breast feeding females.
  5. 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.

Exclusion criteria for monitoring the effects of melatonin

1. All the above PLUS No lying/night time hypertension as determined by 24-hour blood pressure monitoring

Exclusion criteria for healthy controls:

  1. Presence of ANY autonomic dysfunction
  2. Medical therapies or medications which could interfere with testing of autonomic function.
  3. Clinically significant heart disease.
  4. Presence of ANY nerve damage in the peripheral nervous system.
  5. Pregnant or breast feeding females.
  6. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02963181


Locations
Canada, Ontario
University Hospital Recruiting
London, Ontario, Canada, N6A5A5
Contact: Kurt Kimpinski, MD    5196633337    kkimpin@uwo.ca   
Contact: Jacquie Baker, MSc    519-685-8500 ext 73140    jbaker62@uwo.ca   
Sponsors and Collaborators
Lawson Health Research Institute

Publications:

Responsible Party: Lawson Health Research Institute
ClinicalTrials.gov Identifier: NCT02963181     History of Changes
Other Study ID Numbers: 010788
First Posted: November 15, 2016    Key Record Dates
Last Update Posted: March 9, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lawson Health Research Institute:
Melatonin
Yohimbine
Anti-hypertensive agents

Additional relevant MeSH terms:
Hypertension
Hypotension
Nervous System Diseases
Hypotension, Orthostatic
Autonomic Nervous System Diseases
Primary Dysautonomias
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Melatonin
Yohimbine
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Urological Agents