Clinical trial NCT02500628: Heart Rate Variability in Response to Metformin Challenge
Official title: Heart Rate Variability in Response to Metformin Challenge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fibromyalgia
Mitochondrial Diseases
Movement Disorders
Diabetes Mellitus, Type 2
Keywords: metformin
mitochondria
complex 1
fibromyalgia
neurogenic pain
diabetes
tardive dyskinesia
heart rate variability
Lead sponsor: Woodinville Psychiatric Associates
Sponsor class: OTHER
First posted: 2015-07-16
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility 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

Primary outcomes:
measure: Heart Rate Variability (Time Domain)
timeFrame: difference pre/post metformin ingestion (2 hours)
measure: Heart Rate Variability (Frequency Domain)
timeFrame: difference pre/post metformin ingestion (2 hours)
Secondary outcomes:
measure: Number of Patients Reporting Side Effects From the Medication
timeFrame: 2 hours after ingestion
Other outcomes:
Locations:
city: Woodinville
country: United States
facility: Woodinville Psychiatric Associates
state: Washington
Study officials:
affiliation: Woodinville Psychiatric Associates
name: Jon E Berner, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: