Using Droxidopa to treat dysautonomia in adults with Menkes disease and Occipital Horn Syndrome

Phase I/II Study of NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Adults With Occipital Horn Syndrome: Double-blind Placebo-controlled Randomized Crossover Clinical Trial

This study is testing if a medication called Droxidopa can help young adults with Menkes disease or Occipital Horn Syndrome feel better by improving their blood pressure and overall quality of life.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: Nationwide Children's Hospital (Academic / other)
• Locations: 1 site (Columbus, Ohio)
• Trial ID: NCT04977388 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of Droxidopa in young adults who have survived severe complications of Menkes disease or have Occipital Horn Syndrome, both of which can cause dysautonomia symptoms like low blood pressure and dizziness. The study will involve a double-blind, placebo-controlled, randomized crossover design, testing the drug's ability to improve blood pressure and overall quality of life. Participants will be monitored for safety and tolerability while assessing the drug's impact on their symptoms. The goal is to provide insights that could help these patients lead more normal lives.

Who should consider this trial

Good fit: Ideal candidates include young adults with a history of Menkes disease or Occipital Horn Syndrome who experience symptoms of dysautonomia.

Not a fit: Patients without documented mutations in ATP7A or those not experiencing dysautonomia symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients suffering from dysautonomia related to Menkes disease and Occipital Horn Syndrome.

How similar studies have performed: While this approach is novel for these specific conditions, similar studies using Droxidopa for dysautonomia have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. 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.
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. Must sign and date an Informed Consent Form (ICF).
5. Age ≥ 18 years of age.
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 hypertension, anti-hypertensive therapy, heart failure (or decreased ejection fraction), cardiac arrhythmia, or bleeding diatheses.
3. 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.
4. 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

Columbus, Ohio

• Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Stephen G Kaler, MD — Nationwide Children's Hospital
• Study coordinator: Stephen G. Kaler, MD

Conditions Menkes Disease; Occipital Horn Syndrome; Dysautonomia