NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Occipital Horn Syndrome

NCT04977388 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 00001113
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether Northera (Droxidopa) is safe and effective in young adults with Menkes disease who survived the most severe complications of their illness or adults with occipital horn syndrome (OHS), who have trouble with intermittent low blood pressure and other symptoms of dysautonomia. The outcomes and information from this study may help adult survivors of Menkes disease and individuals with OHS lead more normal day-to-day lives.

Conditions

Menkes Disease; Occipital Horn Syndrome

Keywords

Dysautonomia

Outcome Measures

Primary Outcomes (1)

• Treatment Related Adverse Events as Assessed by CTCAE v4.0

  Treatment related adverse events as assessed by CTCAE v 4.0 by study arm

  TEAEs in 6 week periods of either active drug (droxidopa) or placebo

Secondary Outcomes (8)

• Mean Change in Systolic Blood Pressure in Tilt Position

  Change in systolic BP in tilt position during each 6 week treatment arm (droxidopa and placebo) compared to baseline.

• Mean Change in Diastolic Blood Pressure in Tilt Position

  The change in diastolic BP in tilt position during each 6 week treatment arm (droxidopa and placebo) compared to baseline.

• Plasma Catechol Levels

  Change in plasma catechols between each 6 week treatment arm (droxidopa and placebo)

• Change From Baseline in Daily Bowel Movements

  Change from baseline in daily bowel movements per day during each 6 week treatment arm (droxidopa and placebo).

• Change From Baseline in Time Standing Duration

  Change from baseline in standing time duration during each 6 week treatment arm (droxidopa and placebo).

Study Arms (2)

Northera™ (Droxidopa) (Treatment A)

ACTIVE COMPARATOR

Northera (Droxidopa) (Treatment A) will be provided to adult subjects as a capsule with 100mg, 200mg, or 300mg of Northera (Droxidopa) contained within gelatin color capsules (sky blue and white, size 0) based on findings from the dose titration visit. These capsules are physically indistinguishable from the Treatment B (placebo) capsules. Frequency of administration (by mouth) will be twice daily for six weeks.

Drug: Droxidopa

Placebo (Treatment B)

PLACEBO COMPARATOR

Empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from Treatment A capsules. Frequency of administration (by mouth) will be twice daily for six weeks

Other: Placebo

Interventions

Droxidopa DRUG

Subjects will self-administer capsules of Droxidopa by mouth twice daily for six weeks.

Also known as: Northera

Northera™ (Droxidopa) (Treatment A)

Placebo OTHER

Subjects will self-administer capsules of placebo by mouth twice daily for six weeks.

Placebo (Treatment B)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult persons with Menkes disease who survived beyond the expected natural history, attained independent ambulation, attend (or attended) school, and reached adulthood after early CuHis treatment for three years or adults with Occipital Horn Syndrome, 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.
• Must sign and date an Informed Consent Form (ICF).
• Age ≥ 18 years of age.
• 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 hypertension, 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, MD: lead

Study Sites (1)

Vagelos College of Physicians and Surgeons, Columbia University

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Menkes Kinky Hair Syndrome; Occipital horn syndrome; Autonomic Nervous System Diseases

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

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

Limitations and Caveats

No specific study limitations and caveats.

Results Point of Contact

• Title: Stephen G. Kaler MD
• Organization: Vagelos College of Physicians & Surgeons; Columbia University

sgk2141@cumc.columbia.edu

2123053669

Study Officials

• Stephen G Kaler, MD

  Vagelos College of Physicians & Surgeons, Columbia University, New York, NY

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• 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: July 9, 2021
• First Posted: July 26, 2021
• Study Start: July 12, 2021
• Primary Completion: October 30, 2023
• Study Completion: June 29, 2024
• Last Updated: April 13, 2026
• Results First Posted: April 13, 2026

Record last verified: 2026-03

Locations

US (1)