Johns Hopkins University
The goal of this clinical trial is to learn whether guanfacine or cromolyn sodium can improve symptoms and physical functioning in adults with Postural Orthostatic Tachycardia Syndrome (POTS). Both medications are FDA-approved for other conditions but are investigational for the treatment of POTS. The main questions this study aims to answer are: Does treatment with guanfacine or cromolyn sodium improve physical functioning in adults with POTS compared with placebo? Does treatment with guanfacine or cromolyn sodium improve fatigue, cognitive function ("brain fog"), gastrointestinal symptoms, and overall symptom burden in adults with POTS? Researchers will compare guanfacine, cromolyn sodium, and placebo to determine whether either active treatment provides greater improvement in symptoms and physical functioning than placebo. Participants will: Be randomly assigned to receive guanfacine, cromolyn sodium, and placebo during separate 4-week treatment periods in a randomized, double-blind crossover study. Continue standard non-drug POTS management, including recommendations for fluid and salt intake, exercise, compression garments, and other lifestyle measures. Complete questionnaires that measure physical function, fatigue, cognitive symptoms, gastrointestinal symptoms, and overall health throughout the study. Attend scheduled study visits for safety monitoring and assessment of study outcomes. Provide blood, urine, and sputum samples so researchers can evaluate biomarkers related to POTS and better understand how these treatments may work.
Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic disorder of the autonomic nervous system characterized by an excessive increase in heart rate upon standing, accompanied by symptoms such as dizziness, lightheadedness, palpitations, fatigue, cognitive impairment ("brain fog"), gastrointestinal disturbances, exercise intolerance, and reduced quality of life. POTS affects up to 1% of the population, disproportionately impacts women, and has become increasingly recognized following viral illnesses, including COVID-19. Current treatment options consist primarily of lifestyle modificati…
Inclusion Criteria: * Documented diagnosis of POTS per current consensus guidelines: * a heart rate increase of ≥30 bpm within the first 10 minutes of standing or tilt-table testing, without orthostatic hypotension (systolic BP drop ≥20 mmHg) * Frequent symptoms of orthostatic intolerance (e.g., dizziness, palpitations, GI complaints) persisting ≥3 months * Symptom onset within 3 months of a recognized POTS trigger (e.g., infection, vaccination, injury, surgery, pregnancy, or puberty) * Symptomatic response to mediator-targeting medications (e.g., antihistamines, mast cell stabilizers) - also…
Participants receive oral guanfacine for 4 weeks while continuing standardized non-pharmacologic management of POTS. Guanfacine is initiated at 1 mg once daily and may be increased to 2 mg once daily at Week 3 if adequate clinical improvement has not been achieved and the medication is well tolerated. Participants complete symptom assessments and safety evaluations throughout the treatment period.
Participants receive oral cromolyn sodium for 4 weeks while continuing standardized non-pharmacologic management of POTS. Treatment begins at 200 mg twice daily (400 mg/day) and may be increased to 400 mg twice daily (800 mg/day). For participants who tolerate treatment but have an inadequate response, the dose may be further increased to 1,600 mg/day according to the protocol. Symptom assessments and safety evaluations are performed throughout the treatment period.
Participants receive matched placebo for 4 weeks while continuing standardized non-pharmacologic management of POTS. Placebo products are matched to the active study medications, including identical dose-escalation procedures, to maintain blinding. Participants complete the same symptom assessments and safety evaluations as during the active treatment periods.