Gabapentin Treatment of Postural Tachycardia Syndrome (PoTS)

NCT04345432 | Completed

• 1 other identifier: 2013-167
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Postural Orthostatic Tachycardia Syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in Palpitation Awareness and Severity Response

  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

  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

  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)

  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)

Study Arms (2)

Gabapentin

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Gabapentin DRUG

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.

Gabapentin; Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medstar Health Research Institute: lead

Related Publications (14)

• Benarroch EE. Postural tachycardia syndrome: a heterogeneous and multifactorial disorder. Mayo Clin Proc. 2012 Dec;87(12):1214-25. doi: 10.1016/j.mayocp.2012.08.013. Epub 2012 Nov 1.

  PMID: 23122672 BACKGROUND

• Cortez MM, Digre K, Uddin D, Hung M, Blitzer A, Bounsanga J, Voss MW, Katz BJ. Validation of a photophobia symptom impact scale. Cephalalgia. 2019 Oct;39(11):1445-1454. doi: 10.1177/0333102419845641. Epub 2019 May 22.

  PMID: 31116567 BACKGROUND

• Dooley DJ, Taylor CP, Donevan S, Feltner D. Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci. 2007 Feb;28(2):75-82. doi: 10.1016/j.tips.2006.12.006. Epub 2007 Jan 10.

  PMID: 17222465 BACKGROUND

• Drummond PD. A quantitative assessment of photophobia in migraine and tension headache. Headache. 1986 Oct;26(9):465-9. doi: 10.1111/j.1526-4610.1986.hed2609465.x. No abstract available.

  PMID: 3781834 BACKGROUND

• Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz I, Schondorff R, Stewart JM, van Dijk JG. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72. doi: 10.1007/s10286-011-0119-5. No abstract available.

  PMID: 21431947 BACKGROUND

• Gagnon C, Belanger L, Ivers H, Morin CM. Validation of the Insomnia Severity Index in primary care. J Am Board Fam Med. 2013 Nov-Dec;26(6):701-10. doi: 10.3122/jabfm.2013.06.130064.

  PMID: 24204066 BACKGROUND

• Khurana RK. Orthostatic intolerance and orthostatic tachycardia: a heterogeneous disorder. Clin Auton Res. 1995 Feb;5(1):12-8. doi: 10.1007/BF01845493.

  PMID: 7780285 BACKGROUND

• Khurana RK. Experimental induction of panic-like symptoms in patients with postural tachycardia syndrome. Clin Auton Res. 2006 Dec;16(6):371-7. doi: 10.1007/s10286-006-0365-0. Epub 2006 Aug 16.

  PMID: 16915526 BACKGROUND

• Lee KJ, Kim JH, Cho SW. Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2005 Nov 15;22(10):981-8. doi: 10.1111/j.1365-2036.2005.02685.x.

  PMID: 16268973 BACKGROUND

• Lo HS, Yang CM, Lo HG, Lee CY, Ting H, Tzang BS. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol. 2010 Mar-Apr;33(2):84-90. doi: 10.1097/WNF.0b013e3181cda242.

  PMID: 20124884 BACKGROUND

• Nwazue VC, Arnold AC, Raj V, Black BK, Biaggioni I, Paranjape SY, Orozco C, Dupont WD, Robertson D, Raj SR. Understanding the placebo effect in clinical trials for postural tachycardia syndrome. Clin Exp Pharmacol Physiol. 2014 May;41(5):325-30. doi: 10.1111/1440-1681.12221.

  PMID: 24606242 BACKGROUND

• Ross AJ, Ocon AJ, Medow MS, Stewart JM. A double-blind placebo-controlled cross-over study of the vascular effects of midodrine in neuropathic compared with hyperadrenergic postural tachycardia syndrome. Clin Sci (Lond). 2014 Feb;126(4):289-96. doi: 10.1042/CS20130222.

  PMID: 23978222 BACKGROUND

• Wells R, Elliott AD, Mahajan R, Page A, Iodice V, Sanders P, Lau DH. Efficacy of Therapies for Postural Tachycardia Syndrome: A Systematic Review and Meta-analysis. Mayo Clin Proc. 2018 Aug;93(8):1043-1053. doi: 10.1016/j.mayocp.2018.01.025. Epub 2018 Jun 21.

  PMID: 29937049 BACKGROUND

• Zeng Y, Hu D, Yang W, Hayashinaka E, Wada Y, Watanabe Y, Zeng Q, Cui Y. A voxel-based analysis of neurobiological mechanisms in placebo analgesia in rats. Neuroimage. 2018 Sep;178:602-612. doi: 10.1016/j.neuroimage.2018.06.009. Epub 2018 Jun 5.

  PMID: 29883731 BACKGROUND

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Interventions

Gabapentin

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: As each patient is consented, the PI will go to the randomization log which is numbered 1 through 12 and record the subject's study identification number and initials and date in the next available space on the form. He will then remove the large manila envelope in sequence corresponding to the subject's randomization number on the form, open the envelope, and remove the sub-envelope labeled Week 1 Medication. He will remove the packet for Week 1 day 7 and return it to the large envelope. He will then dispense the envelope "Week 1 Medication" containing packets for days 1-6 to the subject. The large manila envelope will then be placed in the subject's study chart until the next visit on Day 7. The PI will provide a photocopy of the randomization log to the independent observer after each patient is randomized. Only the independent observer will have the unblinding code in the event that an emergency situation arises and the code must be broken.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Neurology Division, Department of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 14, 2020
• Study Start: January 1, 2014
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: April 14, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share