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.
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
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
61
500 mg orally after baseline testing of heart rate
Woodinville Psychiatric Associates
Woodinville, Washington, United States
Heart Rate Variability (Time Domain)
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)
Time frame: difference pre/post metformin ingestion (2 hours)
Heart Rate Variability (Frequency Domain)
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.
Time frame: difference pre/post metformin ingestion (2 hours)
Number of Patients Reporting Side Effects From the Medication
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
Time frame: 2 hours after ingestion
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