Gabapentin Treatment of Postural Tachycardia Syndrome (PoTS)

Study Overview
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Brief Summary
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In this pilot study, the investigator will test the usefulness of gabapentin in treating some of the symptoms associated with POTS. Gabapentin is FDA-approved to treat epilepsy and nerve pain and works by reducing excessive activity in the nervous system. This medication has also been shown to be effective in reducing bowel discomfort in patients with irritable bowel syndrome, sleeplessness, and possibly migraine headache. The investigator has observed positive results when prescribing gabapentin off-label to alleviate photosensitivity and headaches in POTS patients. The aim of this pilot study is to better quantify what the investigator has seen and evaluate whether it merits further study in a larger group.

Detailed Description
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Postural orthostatic tachycardia syndrome (POTS) is a disorder of the autonomic nervous system. The autonomic nervous system regulates major bodily functions, such as blood pressure, heart rate, body temperature and sweating. Patients with POTS experience heart palpitations, lightheadedness, and increased heart rate upon standing as well as other symptoms, such as nausea, foggy headedness or inability to concentrate, sensitivity to light, migraine headaches, and trouble sleeping that may occur even when these patients are not standing. Because many POTS symptoms are attributed to excessive activity in parts of the brain, the investigator would like to study whether some of these symptoms can be reduced with a proven seizure medication, gabapentin. The investigator will perform several simple tests on a group of POTS patients both before and after they have been treated with this drug. The tests will include non-invasive heart rate and blood pressure monitoring during a maneuver that requires the participant to exhale in a continuous manner as if blowing up a balloon, an assessment of sensitivity to light, and completion of several questionnaires that assess sleep behavior and sensitivity to heart, bowels, and bladder. Participants will take gabapentin for one week and placebo for another week. Neither the investigator nor the participant will know beforehand whether the participant is taking gabapentin or placebo. The investigator will then compare the results of pre-trial tests to post-trial tests to determine how effective gabapentin was at alleviating symptoms. If the trial is effective, the investigator expects gabapentin to reduce palpitations, decrease sensitivity to light, and improve sleep behavior. Risks of this study may include participants developing side-effects due to the drug. Side-effects of gabapentin may include dizziness, drowsiness, diarrhea, dry mouth, constipation, vomiting, loss of balance, allergic reaction, fatigue, and indigestion. If any side-effects occur, the investigator anticipates that they will be mild because the drug will be administered at a very low dose. Any side-effects that occur are expected to resolve quickly after stopping the medication. Furthermore, by gradually increasing the dose and restricting the trial to a relatively short period of time, the investigator will limit the risk of side-effects. Doctors and patients alike could benefit from this study by learning about a new use for an established drug to treat several of the symptoms of POTS, thereby improving patients' quality of life.

Official Title
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Gabapentin Treatment of Postural Tachycardia Syndrome (PoTS): a Pilot Study

Conditions
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Postural Orthostatic Tachycardia Syndrome

Intervention / Treatment
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* Drug: Gabapentin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults between the ages of 18 and 60 years of age For women of childbearing age, no missed menstrual cycles Diagnosis of POTS confirmed by the PI after autonomic function tests Able to discontinue GABAergic drugs, beta blockers, and sleep medication for one week before study start-up and for the duration of the study Able to read and understand English Exclusion Criteria: Men and women under 18 and over 60 years of age Unable to read or understand English A history of gastroparesis, renal or hepatic dysfunction, cardiac arrhythmias, eye disorders and sleep apnea

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Consented patients are randomized into one of two groups using balanced permutations generated randomization.com. Subject numbers will be ordered and placed in individually numbered, nontransparent envelopes by an independent observer. Trial medication is administered based on the randomization scheme. Baseline data will be collected followed by a 7-day trial phase of either gabapentin or placebo on a gradually increasing dosing schedule. Post-trial data will be collected on day 7 followed by 1-week washout period and Week 3 crossover medication.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gabapentin<br>The experiment will be divided into the following phases: Baseline phase - Demographic and test data will be collected prior to dispensing trial medication using all measures listed above 7 day trial phase with gradual increase of dose from 100 mg/day to 600 mg/day (300 b.i.d) on day 6 of gabapentin or placebo. A single morning dose (300 mg) will be given at the lab on day 7 followed by post-trial testing (using above measures) 1 hour after drug administration. 7 day drug washout phase - no medication will be taken 7 day crossover trial phase - baseline measurements will be repeated and groups will switch to gabapentin or placebo. Post-trial measurements will be taken 1 hour after a single morning dose (300 mg) on day 7. Follow-up phone call - Patients will be called 8-10 days after completion of study to ensure that there have been no unexpected events. | Drug: Gabapentin<br>* Gradually increasing doses of medication from 100 mg on day 1 to 300 mg twice a day on day 6. On day 7, the patient received a 300-mg dose from the day 7 envelope, about two hours after a light breakfast and 1 hour before data collection. The relatively low dose and gradual titration were selected to enhance compliance and reduce adverse effects, based on a rectal mechanosensitivity study.<br>|
| Placebo Comparator: Placebo<br>The experiment will be divided into the following phases: Baseline phase - Demographic and test data will be collected prior to dispensing trial medication using all measures listed above 7 day trial phase with gradual increase of dose from 100 mg/day to 600 mg/day (300 b.i.d) on day 6 of gabapentin or placebo. A single morning dose (300 mg) will be given at the lab on day 7 followed by post-trial testing (using above measures) 1 hour after drug administration. 7 day drug washout phase - no medication will be taken 7 day crossover trial phase - baseline measurements will be repeated and groups will switch to gabapentin or placebo. Post-trial measurements will be taken 1 hour after a single morning dose (300 mg) on day 7. Follow-up phone call - Patients will be called 8-10 days after completion of study to ensure that there have been no unexpected events. | Drug: Gabapentin<br>* Gradually increasing doses of medication from 100 mg on day 1 to 300 mg twice a day on day 6. On day 7, the patient received a 300-mg dose from the day 7 envelope, about two hours after a light breakfast and 1 hour before data collection. The relatively low dose and gradual titration were selected to enhance compliance and reduce adverse effects, based on a rectal mechanosensitivity study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Acute Panic Inventory (API) | Acute Panic Inventory is a validated 17-item (4 psychological and 13 somatic/visceral) questionnaire. Patients rate each item on a 4-point severity scale of 0 to 3, yielding a score of 0-51. An increase in API score >13 over baseline or a total score of >20 distinguished panic subjects from controls. | at baseline, at 1 week from baseline (upon completion of first treatment), at 2 weeks from baseline (upon completion of washout period), at 3 weeks from baseline (upon completion of second treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Palpitation Awareness and Severity Response | In the Palpitation Awareness and Severity Response, the patient identifies one or more of the eight types of palpitations and grades their severity (1-10) immediately after the Valsalva maneuver (expiratory strain of 40 mm Hg for 15 seconds). | at baseline, at 1 week from baseline (upon completion of first treatment), at 2 weeks from baseline (upon completion of washout period), at 3 weeks from baseline (upon completion of second treatment) | 
| Change in Insomnia Severity Index | Insomnia Severity Index is a validated 7-item questionnaire rating severity of insomnia on a 5-point (zero to 4) scale yielding a score of 0-28, with a score of >14 indicating insomnia. | at baseline, at 1 week from baseline (upon completion of first treatment), at 2 weeks from baseline (upon completion of washout period), at 3 weeks from baseline (upon completion of second treatment) | 
| Change in Photosensitivity Index | The Photosensitivity Index is a 10-point visual analog of scale yielding a score of 0-10 to rate glare and pain after 30-second exposure of ophthalmoscopic light in each eye in a dimly lit room. Higher score indicates greater sensitivity to light. | at baseline, at 1 week from baseline (upon completion of first treatment), at 2 weeks from baseline (upon completion of washout period), at 3 weeks from baseline (upon completion of second treatment) | 
| Change in Somatosensory Amplification Scale (SSAS) | The Somatosensory Amplification Scale is a validated 5-point severity scale used to investigate the possibility of perceptual amplification of symptoms. The scale covers 10 somatic and visceral sensations to quantify symptom amplification yielding a score of 0-50, with higher score indicating greater somatosensory amplification. A score >30 may reflect a highly somatizing condition. | at baseline, at 1 week from baseline (upon completion of first treatment), at 2 weeks from baseline (upon completion of washout period), at 3 weeks from baseline (upon completion of second treatment) |