Recruiting
Phase 1
Phase 2

Droxidopa

Sponsor:

Stephen G. Kaler

Code:

NCT07398508

Conditions

Menkes Disease

Eligibility Criteria

Sex: All

Age: 7 - 17

Healthy Volunteers: Not accepted

Interventions

Droxidopa Oral Product

Placebo Control

Study Details

Brief summary:

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.

Conditions

Menkes Disease

Study ID

NCT07398508

Start date

Aug 10, 2026

Status verified date

Jul, 2026

Completion date

Jun 30, 2030

Anticipated

Primary completion date

Jun 30, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 7 - 17

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

6 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Droxidopa Treatment Arm

Oral administration of droxidopa study drug.

placebo comparator: Placebo Control Arm

Oral administration of placebo control capsules that are indistinguishable from study drug.

Interventions

Droxidopa Oral Product

1 month supply will contain pre-prepared capsules containing either 20mg, 40mg, or 60mg Droxidopa, plus 300 ml of simple syrup. For each dose, add the contents of 1 capsule and 10 ml of simple syrup to a plastic 1 ounce medication cup. Simple syrup will be dispensed from a larger bottle using a 10mL syringe. Mix by swirling briefly and consume the entire contents. Prepare the suspension freshly for each dose and take the prescribed dose twice daily, at approximately 8am and 2pm.

Placebo Control

1 month supply will contain pre-prepared capsules containing cellulose microcrystalline placebo, plus 300 ml of simple syrup. For each dose, add the contents of 1 capsule and 10 ml of simple syrup to a plastic 1 ounce medication cup. Simple syrup will be dispensed from a larger bottle using a 10mL syringe. Mix by swirling briefly and consume the entire contents. Prepare the suspension freshly for each dose and take the prescribed dose twice daily, at approximately 8am and 2pm.

Primary outcome measure

  • Incidence of SAEs [ Time Frame: 10 weeks ]

Central Contacts and Locations

Central contacts

Stephen G Kaler, MD, MPH

212 305-3669sgk2141@cumc.columbia.edu

Locations

Vagelos College of Physicians and Surgeons, Columbia University

Recruiting

New York, New York, United States, 10032

Contacts

Stephen G Kaler, MD

212 305-3669sgk2141@cumc.columbia.edu

Maryann Kaler, MS

mk5169@cumc.columbia.edu

Principal Investigator:

Stephen G Kaler, MD

More Information

Sponsor

Stephen G. Kaler

Last update posted

Jul 20, 2026

Last verified

Jul, 2026

Keywords

  • Menkes disease
  • dysautonomia
  • orthostatic hypotension

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Stephen G. Kaler on 2026-07-20.