NORTHERA (DROXIDOPA) for Dysautonomia in Pediatric Survivors of Menkes Disease

Recruiting now · Phase 1/Phase 2 · Has a placebo group

Conditions studied: Menkes Disease

In brief

This clinical trial will evaluate the safety, tolerability, dosing, and efficacy of Northera (Droxidopa) in children with Menkes disease aged 7 to 17 years who survived the major neurodegenerative and neurocognitive effects of Menkes disease through early Copper Histidinate treatment. The investigator hypothesizes that Northera (Droxidopa) treatment in pediatric Menkes disease survivors with symptoms of dysautonomia (e.g., syncope, dizziness, orthostatic hypotension, abnormal sinoatrial conduction, and bowel or bladder dysfunction) from deficiency of the cuproenzyme, dopamine-beta-hydroxylase, will be safe and will correct or improve blood neurochemical levels, raise systolic blood pressure, and produce symptomatic improvement and a better quality of life. The investigator will test this hypothesis, in six to ten child or adolescent Menkes disease survivors through a placebo-controlled trial to evaluate adverse event rates and whether oral administration of Northera (Droxidopa) at doses established for individual subjects by careful dose titration improves plasma norepinephrine and dihydroxyphenylglycol (DHPG) levels, raises systolic blood pressure, and improves performance on tests of physical exertion. As an exploratory outcome measure, the study will validate the Orthostatic Hypotension Symptom Assessment (OHSA) questionnaire for this population for two four-week periods of either active or placebo treatment. Aim 1. Determine the safety of Droxidopa in Menkes disease pediatric survivors. Aim 2. Determine the efficacy of Droxidopa in Menkes disease survivors. The investigator hypothesizes that low-dose Droxidopa treatment in classic Menkes disease survivors aged 7 to 17 will improve orthostatic hypotension and ameliorate other signs and symptoms of dysautonomia. This pilot study will employ an ascending dose paradigm in a double-blind placebo-controlled randomized crossover design to optimize statistical power and rigorously discern treatment effects on 1) tilt table tests of orthostatic hypotension, 2) systolic and diastolic blood pressure, 3) plasma neurochemical levels and 4) tests of physical exertion. The trial will also validate the Orthostatic Hypotension Symptom Assessment (OHSA) questionnaire for this population of children and adolescents. This study addresses an important unmet clinical need for subjects with a rare disease, Menkes disease.

Key facts

Study ID

NCT07398508

Run by

Stephen G. Kaler

People needed

6

Starts

2026-08-10

Expected to finish

2030-06-30

Last updated by the study team

2026-07-20

Who can join

Age: 7 and older, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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.
• Documented mutation in ATP7A.
• One parent must sign and date an Informed Consent Form (ICF) and patient must also assent.
• Age 7 to 17 years. (Enrollment will be staggered so that at least the first two children enrolled are aged 12-17 years.)
• Ability to adhere to the prescribed oral Northera (Droxidopa) regimen.
• Willingness to comply with all study visits and procedures.

You may not qualify if…

• Pre-existing liver (e.g., hepatitis, biliary atresia, cirrhosis) or kidney disease (i.e., calculated glomerular filtration rate <30 ml/min).
• History of age-adjusted stage 1 hypertension (≥ 95th percentile) [1] (Also see Attachment A).
• History of anti-hypertensive therapy, heart failure (or decreased ejection fraction), cardiac arrhythmia, or bleeding diatheses.
• 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.
• Any alpha-1 adrenoreceptor agonist, beta-blocker, DOPA decarboxylase inhibitor, midodrine, ephedrine, or any triptan medication as a concomitant medication.

Where it is running

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

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.