Heart Rate Variability in Response to Metformin Challenge

December 30, 2017 updated by: Jon Berner MD PhD, Woodinville Psychiatric Associates
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

61

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Woodinville, Washington, United States, 98072
        • Woodinville Psychiatric Associates

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Glucophage

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
difference pre/post metformin ingestion (2 hours)
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.
difference pre/post metformin ingestion (2 hours)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 hours after ingestion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Woodinville Psychiatric Associates

Investigators

  • Principal Investigator: Jon E Berner, MD PhD, Woodinville Psychiatric Associates

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

February 1, 2016

Study Completion (Actual)

February 1, 2016

Study Registration Dates

First Submitted

July 11, 2015

First Submitted That Met QC Criteria

July 14, 2015

First Posted (Estimate)

July 16, 2015

Study Record Updates

Last Update Posted (Actual)

January 3, 2018

Last Update Submitted That Met QC Criteria

December 30, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20150618

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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