Phase I/II Study of NORTHERA (DROXIDOPA) for Dysautonomia in Pediatric Survivors of Menkes Disease.

NCT07398508 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ACYY0326
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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

Keywords

Menkes disease, dysautonomia, orthostatic hypotension

Outcome Measures

Primary Outcomes (1)

• Incidence of SAEs

  This is to measure safety and tolerability of study drug in children and adolescents with Menkes disease. The study will determine the adverse event profile of the formulation by comparing the time-to-event of serious adverse events (SAEs) and adverse events (AEs) between treatment and placebo arms as defined in the protocol.

  10 weeks

Secondary Outcomes (5)

• Change in level of plasma norepinephrine and dihydroxyphenylglycol after Northera (Droxidopa)

  Baseline and post intervention at 4 weeks

• Change in systolic blood pressure

  Baseline and post intervention at 4 weeks

• Average number of daily bowel movements

  Baseline, 4 weeks

• Average time standing

  Baseline and post intervention at 4 weeks

• Average 6-minute walk distance

  Baseline and post intervention at 4 weeks

Other Outcomes (1)

• Change in scores on the Orthostatic Hypotension Symptom Assessment questionnaire after Northera (Droxidopa)

  Baseline and post intervention at 4 weeks

Study Arms (2)

Droxidopa Treatment Arm

EXPERIMENTAL

Oral administration of droxidopa study drug.

Drug: Droxidopa Oral Product

Placebo Control Arm

PLACEBO COMPARATOR

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

Other: Placebo Control

Interventions

Droxidopa Oral Product DRUG

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.

Also known as: NORTHERA

Droxidopa Treatment Arm

Placebo Control OTHER

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.

Also known as: Placebo pill

Placebo Control Arm

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

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.

Sponsors & Collaborators

• Stephen G. Kaler: lead

Study Sites (1)

Vagelos College of Physicians and Surgeons, Columbia University

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Menkes Kinky Hair Syndrome; Autonomic Nervous System Diseases; Hypotension, Orthostatic

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Hair Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Orthostatic Intolerance; Primary Dysautonomias; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Stephen G Kaler, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen G Kaler, MD, MPH

CONTACT

212 305-3669; sgk2141@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Double-blind Placebo-controlled Randomized Crossover Clinical Trial

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 10, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

US (1)