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

Stephen G. Kaler, MD3 enrolled

Overview

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.

This pilot clinical trial will evaluate the safety, tolerability, dosing, and preliminary efficacy of Northera (Droxidopa) treatment in young adults who survived the major neurodegenerative and neurocognitive effects of Menkes disease through early Copper Histidinate treatment. We hypothesize that Northera (Droxidopa) in Menkes disease survivors with symptoms of dysautonomia (e.g., syncope, dizziness, orthostatic hypotension, abnormal sinoatrial conduction, nocturnal bradycardia, and bowel or bladder dysfunction) from persistent deficiency of the copper-dependent enzyme, dopamine-β-hydroxylase, will be safe, and correct or improve blood neurochemical levels, raise systolic blood pressure, and produce symptomatic improvement and better overall quality of life. We will test this hypothesis in six to ten Menkes disease survivors or OHS patients in a double-blind placebo-controlled randomized crossover clinical trial.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Menkes Disease Occipital Horn Syndrome

Interventions

DroxidopaDRUG

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

PlaceboOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 Years

Medical Language ↔ Plain English

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.

Locations (1)

Vagelos College of Physicians and Surgeons, Columbia University

New York, New York, United States

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5 tool

Grade 1-5 with increasing severity from 1 to 5

Time frame: Six week periods of Active drug versus Placebo