Diabetes Mellitus, Type 2, Fibromyalgia, Mitochondrial Diseases, Movement Disorders
Conditions
Keywords
metformin, mitochondria, complex 1, fibromyalgia, neurogenic pain, diabetes, tardive dyskinesia, heart rate variability
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.
Interventions
DRUGMetformin
500 mg orally after baseline testing of heart rate
Sponsors
Woodinville Psychiatric Associates
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heart Rate Variability (Time Domain) | 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) |
| Heart Rate Variability (Frequency Domain) | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Reporting Side Effects From the Medication | 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 |
Countries
United States
Participant flow
Recruitment details
7/25/2015 to 2/21/16
Participants by arm
| Arm | Count |
|---|---|
| Fibromyalgia Fibromyalgia (subgroups: opioid responsive, opioid resistant, opioid intolerant) Metformin 500 mg po in AM
Metformin: 500 mg po after baseline testing of heart rate | 38 |
| Antipsychotic Use Antipsychotic use (subgroups: no side effects, dyskinesia, weight gain) Metformin 500 mg po in AM
Metformin: 500 mg po after baseline testing of heart rate | 23 |
| Total | 61 |
Baseline characteristics
| Characteristic | Antipsychotic Use | Total | Fibromyalgia |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 60 Participants | 37 Participants |
| Age, Continuous | 47.61 years STANDARD_DEVIATION 11.9 | 47.1 years STANDARD_DEVIATION 12.32 | 46.71 years STANDARD_DEVIATION 12.15 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 23 Participants | 61 Participants | 38 Participants |
| Sex: Female, Male Female | 20 Participants | 51 Participants | 31 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 23 |
| other Total, other adverse events | 13 / 38 | 9 / 23 |
| serious Total, serious adverse events | 0 / 38 | 0 / 23 |
Outcome results
Primary
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)
Population: patients with or without fibromyalgia. with or without antipsychotic use
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fibromyalgia | Heart Rate Variability (Frequency Domain) | -.14 ratio | Standard Deviation 0.29 |
| Antipsychotic Use | Heart Rate Variability (Frequency Domain) | -.24 ratio | Standard Deviation 0.38 |
p-value: 0.27t-test, 2 sided
Primary
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)
Population: Patients with or without fibromyalgia, with or without antipsychotic use.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fibromyalgia | Heart Rate Variability (Time Domain) | 0.92 msec/msec | Standard Deviation 0.31 |
| Antipsychotic Use | Heart Rate Variability (Time Domain) | 0.83 msec/msec | Standard Deviation 0.32 |
Comparison: comparison between fibromyalgia and non-fibromyalgia groupp-value: 0.77t-test, 2 sided
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fibromyalgia | Number of Patients Reporting Side Effects From the Medication | 13 Participants |
| Antipsychotic Use | Number of Patients Reporting Side Effects From the Medication | 9 Participants |
Comparison: difference between fibromyalgia and non-fibromyalgia patients.p-value: 0.92t-test, 2 sided