Guanfacine and Cromolyn Sodium for POTS: The DBPOTS Trial

NCT07757555 | Not Yet Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: IRB00522911151749/ 90118971
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Postural Orthostatic Tachycardia Syndrome (POTS); Dysautonomia; Orthostatic Intolerance; Autonomic Nervous System Disorders; Hyperadrenergic POTS; Adult POTS; Guanfacine; Cromolyn Sodium; Re-purposed FDA-approved drugs; Sympatholytic therapy; Placebo-Controlled; Phase II Exploratory Trial; Comparative Effectiveness; Autonomic Dysfunction; Voltage-Gated Sodium Channels; SCN9A; SCN10A; NaV Channels; Ion Channelopathy; Cognitive Dysfunction; Brain Fog; Fatigue

Outcome Measures

Primary Outcomes (1)

• Change in Physical Function as Measured by the PROMIS® Physical Function Scale

  Scores are reported as T-scores based on a U.S. population average of 50, with a standard deviation of 10. Higher scores indicate better physical function.

  Week 0 (baseline), Week 4 (end of treatment), week 10 (end of treatment), week 16 (end of treatment)

Secondary Outcomes (5)

• Patient-Reported Outcomes Measurement Information System (PROMIS®) Fatigue

  Week 0 (baseline), Week 4 (end of treatment), week 10 (end of treatment), week 16 (end of treatment)

• Patient-Reported Outcomes Measurement Information System (PROMIS®) Cognitive Function

  Week 0 (baseline), Week 4 (end of treatment), Week 10 (end of treatment), Week 16 (end of treatment)

• Clinical Global Impressions (CGI)

  Week 0 (baseline), Week 4 (end of treatment), Week 10 (end of treatment), Week 16 (end of treatment)

• Malmö Postural Orthostatic Tachycardia Syndrome Symptom Score

  Week 0 (baseline), Week 4 (end of treatment), Week 10 (end of treatment), and Week 16 (end of treatment)

• Patient-Reported Outcomes Measurement Information System (PROMIS®) Gastrointestinal Symptom Scale

  Week 0 (baseline), Week 4 (end of treatment), Week 10 (end of treatment), Week 16 (end of treatment)

Study Arms (3)

Guanfacine

EXPERIMENTAL

Participants receive oral guanfacine during one 4-week treatment period, with dose escalation permitted according to protocol if clinically indicated.

Drug: Guanfacine (GFC); Drug: Cromolyn Sodium; Drug: Placebo

Cromolyn Sodium

EXPERIMENTAL

Participants receive oral cromolyn sodium during one 4-week treatment period, with protocol-defined dose escalation if needed.

Drug: Guanfacine (GFC); Drug: Cromolyn Sodium; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Participants receive matched placebo during one 4-week treatment period to maintain blinding.

Drug: Guanfacine (GFC); Drug: Cromolyn Sodium; Drug: Placebo

Interventions

Guanfacine (GFC) DRUG

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.

Cromolyn Sodium; Guanfacine; Placebo

Cromolyn Sodium DRUG

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.

Cromolyn Sodium; Guanfacine; Placebo

Placebo DRUG

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.

Cromolyn Sodium; Guanfacine; Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 eligible
• Presence of flushing, pruritis, urticaria, or angioedema - also eligible
• Alternative diagnoses must be excluded via prior clinical workup and laboratory assessment

You may not qualify if:

• Alternative medical causes for symptoms, including:
• Anemia,
• Active infection,
• Dehydration,
• Hyperthyroidism,
• Pheochromocytoma,
• Adrenal insufficiency,
• Paraneoplastic conditions
• Active neurologic disease (including stroke and epilepsy)
• Prolonged immobilization
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Johns Hopkins University: lead
• Dysautonomia International: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Autonomic Nervous System Diseases; Orthostatic Intolerance; Primary Dysautonomias; Cognitive Dysfunction; Mental Fatigue; Fatigue

Interventions

Guanfacine; Cromolyn Sodium

Condition Hierarchy (Ancestors)

Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Malcolm Brock, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen Rodgers, BS

CONTACT

410-955-9047; kpelosk1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to one of six possible treatment sequences, so the order in which the participants receive the interventions differs between participants. Each treatment period lasts 4 weeks and is separated by a 2-week washout period to minimize carryover effects. This allows each participant to serve as own control, reducing variability and improving the ability to compare treatments.

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 11, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): February 2, 2028
• Last Updated: August 11, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)