Northera (droxidopa) for dysautonomia in children who survived Menkes disease

Phase I/II Study of NORTHERA (DROXIDOPA) for Dysautonomia in Pediatric Survivors of Menkes Disease: Double-blind Placebo-controlled Randomized Crossover Clinical Trial.

This trial will test whether the oral medicine Northera (droxidopa) is safe and helps reduce fainting, dizziness, low blood pressure, and other dysautonomia symptoms in children and adolescents (ages 7–17) who survived Menkes disease after early copper treatment.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 7 Years to 17 Years
• Sex: All
• Sponsor: Columbia University (other)
• Locations: 1 site (New York, New York)
• Trial ID: NCT07398508 on ClinicalTrials.gov

What this trial studies

This Phase I/II, placebo-controlled trial will enroll about six to ten pediatric Menkes disease survivors to study safety, tolerability, dosing, and preliminary efficacy of oral droxidopa. Participants must be aged 7–17, have a documented ATP7A mutation, have survived following early copper histidinate treatment, and show clinical signs of dysautonomia such as orthostatic hypotension, frequent dizziness, or chronic diarrhea. The study will compare droxidopa versus placebo, monitor adverse events, measure blood neurochemistry and systolic blood pressure, and record symptomatic and quality-of-life changes. Results will inform whether droxidopa corrects neurochemical deficits, raises blood pressure, and produces clinically meaningful symptom improvement in this population.

Who should consider this trial

Good fit: Ideal candidates are ambulatory children or adolescents aged 7–17 with Menkes disease who received early copper histidinate, have a documented ATP7A mutation, attend school, and have recurrent symptoms of dysautonomia such as orthostatic hypotension, frequent dizziness, or chronic diarrhea.

Not a fit: Patients without dysautonomia symptoms, those outside the 7–17 age range, nonambulatory individuals, or those with contraindications to droxidopa or without prior early copper treatment are unlikely to benefit from this specific trial.

Why it matters

Potential benefit: If successful, Northera could raise blood pressure, reduce episodes of fainting and dizziness, and improve daily functioning and quality of life for pediatric Menkes survivors with dysautonomia.

How similar studies have performed: Droxidopa has demonstrated benefit for neurogenic orthostatic hypotension in adults, but its use specifically in pediatric Menkes survivors is novel and has not been established in larger studies.

Eligibility criteria

Inclusion Criteria:

1. Children or adolescents with Menkes disease who survived beyond the expected natural history, attained independent ambulation, and attend school after early CuHis treatment for three years, who manifest clinical signs and symptoms of dysautonomia, e.g., orthostatic hypotension: specifically, a decrease in systolic or diastolic blood pressure of at least 20 or 10 mm Hg, respectively, within three minutes after standing, and/or chronic diarrhea: production of loose stools with or without increased stool frequency for more than four weeks immediately preceding enrollment.
2. History of at least thrice weekly occurrence of dizziness/feeling lightheaded while standing upright and/or thrice weekly episodes of diarrhea or an urgent need to defecate after food ingestion for more than four weeks immediately preceding enrollment.
3. Documented mutation in ATP7A.
4. One parent must sign and date an Informed Consent Form (ICF) and patient must also assent.
5. Age 7 to 17 years. (Enrollment will be staggered so that at least the first two children enrolled are aged 12-17 years.)
6. Ability to adhere to the prescribed oral Northera (Droxidopa) regimen.
7. Willingness to comply with all study visits and procedures.

Exclusion Criteria:

1. Pre-existing liver (e.g., hepatitis, biliary atresia, cirrhosis) or kidney disease (i.e., calculated glomerular filtration rate \<30 ml/min).
2. History of age-adjusted stage 1 hypertension (≥ 95th percentile) \[1\] (Also see Attachment A).
3. History of anti-hypertensive therapy, heart failure (or decreased ejection fraction), cardiac arrhythmia, or bleeding diatheses.
4. Any disease or condition that, in the opinion of the Investigator, has a high probability of precluding the subject from completing the study or where the subject cannot or will not appropriately comply with study requirements.
5. Any alpha-1 adrenoreceptor agonist, beta-blocker, DOPA decarboxylase inhibitor, midodrine, ephedrine, or any triptan medication as a concomitant medication.

Where this trial is running

New York, New York

• Vagelos College of Physicians and Surgeons, Columbia University — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Stephen G Kaler, MD, MPH — Columbia University
• Study coordinator: Stephen G Kaler, MD, MPH

Conditions: Menkes Disease, Menkes disease, dysautonomia, orthostatic hypotension