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

Menkes Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04977388
• Other study ID #: 00001113
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 12, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: May 2024
• Source: Nationwide Children's Hospital
• Contact: Stephen G. Kaler, MD
• Phone: 614 722-5964
• Email: stephen.kaler[@]nationwidechildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autonomic Nervous System Diseases
• Cutis Laxa
• Ehlers-Danlos Syndrome
• Menkes Disease
• Occipital Horn Syndrome
• Primary Dysautonomias
• Syndrome

Intervention

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

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

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Stephen G. Kaler, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in scores on the Orthostatic Hypotension Symptom Assessment questionnaire after Northera (Droxidopa)	Scores range from zero to 10 with 0 meaning no symptoms and 10 meaning the worst possible symptoms	Six week periods of active drug versus placebo
Primary	Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5 tool	Grade 1-5 with increasing severity from 1 to 5	Six week periods of Active drug versus Placebo
Secondary	Change in plasma catechol levels after Northera (Droxidopa)	Serial determinations of norepinephrine and dihydroxyphenylglycol	Six week periods of active drug versus placebo
Secondary	Changes in systolic blood pressure after Northera (Droxidopa)	Serial BP measurements including at-home monitoring	Six week periods of active drug versus placebo
Secondary	Changes in gastrointestinal symptoms after Northera (Droxidopa)	As reflected in the Irritable Bowel Syndrome-Diarrhea report	Six week periods of active drug versus placebo
Secondary	Changes in Time standing duration after Northera (Droxidopa)	Measured in time seconds	Six week periods of active drug versus placebo
Secondary	Changes in Up and Go test performance after Northera (Droxidopa)	Measured in time (seconds) needed to stand up from a chair, walk 3 m and return to a seated position on the chair.	Six week periods of active drug versus placebo
Secondary	Changes in 6 minute walk test performance after Northera (Droxidopa)	Measured in distance (meters) walked in 6 minutes	Six week periods of active drug versus placebo