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Heart Rate Variability in Response to Metformin Challenge

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ClinicalTrials.gov Identifier: NCT02500628
Recruitment Status : Completed
First Posted : July 16, 2015
Results First Posted : January 3, 2018
Last Update Posted : January 3, 2018
Sponsor:
Information provided by (Responsible Party):
Jon Berner MD PhD, Woodinville Psychiatric Associates

Brief Summary:
Diseases caused by brain energy supply defects can be innate (fibromyalgia secondary to familial mitochondrial disorders) or acquired (tardive dyskinesia or weight gain associated with prolonged antipsychotic use). Patients with these possible mitochondrial disorders will provide a baseline resting heart rate sample, ingest low-dose metformin (500 mg), and then provide an additional sample 2 hours later.

Condition or disease Intervention/treatment Phase
Fibromyalgia Mitochondrial Diseases Movement Disorders Diabetes Mellitus, Type 2 Drug: Metformin Phase 2

Detailed Description:

Doctors need to develop tests which inexpensively and reliably evaluates brain metabolism. Current diagnostic tests sample other tissues which often run on different fuels (fats), utilize unproven and often insensitive brain imaging scanners, or sequence thousands to millions of base-pairs of DNA. All of these tests are expensive. None of these tests accurately or completely capture the interactions between the 1000s of proteins involved in brain metabolism.

The investigators suspect that mathematical analysis of the resting heart rate may provide some insight into brain metabolism. The brain controls heart rate in response to changes in blood pressure and blood gases like carbon dioxide and oxygen. Tight control of heart rate is necessary to make sure that the brain has the right mix of fuel and air. Because the brain can't respond instantly to changes in its fuel supply, this system acting as a biological carburetor has a natural oscillatory rhythm that can be monitored just like frequencies on the radio.

The investigators propose to amplify these rhythms by modestly metabolically stressing the brain with metformin, a inhibitor of complex 1 in the mitochondria.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Heart Rate Variability in Response to Metformin Challenge
Study Start Date : July 2015
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016


Arm Intervention/treatment
Experimental: Fibromyalgia
Fibromyalgia (subgroups: opioid responsive, opioid resistant, opioid intolerant) Metformin 500 mg orally in the morning
Drug: Metformin
500 mg orally after baseline testing of heart rate
Other Name: Glucophage

Experimental: Antipsychotic use
Antipsychotic use (subgroups: no side effects, dyskinesia, weight gain) Metformin 500 mg orally in the morning
Drug: Metformin
500 mg orally after baseline testing of heart rate
Other Name: Glucophage




Primary Outcome Measures :
  1. Heart Rate Variability (Time Domain) [ Time Frame: difference pre/post metformin ingestion (2 hours) ]
    ratio of the standard deviation of sampled intervals between each heart beat for ten minutes at time 1 (prior to metformin ingestion) over standard deviation of the sampled intervals between each heart beat for ten minutes at time 2 (2 hours post metformin ingestion)

  2. Heart Rate Variability (Frequency Domain) [ Time Frame: difference pre/post metformin ingestion (2 hours) ]
    total power in the frequency domain is estimated for 10 minutes prior to metformin ingestion and then divided by the total power in the frequency domain estimated for 10 minutes 2 hours after metformin ingestion. Ratio is log-transformed.


Secondary Outcome Measures :
  1. Number of Patients Reporting Side Effects From the Medication [ Time Frame: 2 hours after ingestion ]
    Patient after testing generated an unprompted list of observed side effects from the medication. Many reported none. Results were scored as the binary presence or absence of side effect



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

EITHER chronic neurogenic pain meeting American College of Rheumatology criteria for fibromyalgia or previous/current exposure to antipsychotic medications

Exclusion Criteria:

  • recent infection,
  • renal failure,
  • pre-existing cardiac disease,
  • chronic obstructive pulmonary disease
  • inability to participate in informed consent,
  • lack of transport to return home from study site,
  • severe fasting intolerance or hypoglycemia,
  • history of stroke-alike episode,
  • uncontrolled migraine or cyclic vomiting,
  • diabetes on insulin or sulfonylurea,
  • non-English speaker,
  • medications with strong effects on baseline heart rate variability

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): NCT02500628


Locations
United States, Washington
Woodinville Psychiatric Associates
Woodinville, Washington, United States, 98072
Sponsors and Collaborators
Woodinville Psychiatric Associates
Investigators
Principal Investigator: Jon E Berner, MD PhD Woodinville Psychiatric Associates

Responsible Party: Jon Berner MD PhD, Clinic Director, Woodinville Psychiatric Associates
ClinicalTrials.gov Identifier: NCT02500628     History of Changes
Other Study ID Numbers: 20150618
First Posted: July 16, 2015    Key Record Dates
Results First Posted: January 3, 2018
Last Update Posted: January 3, 2018
Last Verified: December 2017

Keywords provided by Jon Berner MD PhD, Woodinville Psychiatric Associates:
metformin
mitochondria
complex 1
fibromyalgia
neurogenic pain
diabetes
tardive dyskinesia
heart rate variability

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Fibromyalgia
Myofascial Pain Syndromes
Movement Disorders
Mitochondrial Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Central Nervous System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs