Guanfacine and Cromolyn Sodium for POTS: The DBPOTS Trial

Summary

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.

Conditions

• Postural Orthostatic Tachycardia Syndrome (POTS)
• Dysautonomia
• Orthostatic Intolerance
• Autonomic Nervous System Diseases

Interventions

DRUG

Guanfacine (GFC)

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.

DRUG

Cromolyn Sodium

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.

DRUG

Placebo

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.

Sponsors & Collaborators

• Dysautonomia International

  collaborator OTHER

• Johns Hopkins University

  lead OTHER

Principal Investigators

• Malcolm Brock, MD · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-15

Primary Completion

2027-12-15

Completion

2028-02-02

FDA Drug

Yes

Countries

• United States

Study Locations