Menkes DiseasePhase 1/2NCT04977388
NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Occipital Horn Syndrome
A Phase 1/2 study testing Droxidopa in people with Menkes Disease and Occipital Horn Syndrome, run by Stephen G. Kaler, MD at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Menkes Disease, Occipital Horn Syndrome
- What is being tested?
- Droxidopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jul 2021to 29 Jun 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vagelos College of Physicians and Surgeons, Columbia University
New York, New York, 10032
About this study
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
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.
Read the detailed 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.
- Conditions
- Menkes Disease, Occipital Horn Syndrome
- Being tested
- Droxidopa, Placebo
- Keywords
- Dysautonomia
- Medical subject headings
- Menkes Kinky Hair Syndrome, Occipital horn syndrome, Autonomic Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
Also called Northera
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Related Adverse Events as Assessed by CTCAE v4.0
Treatment related adverse events as assessed by CTCAE v 4.0 by study arm
Measured: 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 treatment arm (droxidopa and placebo) compared to baseline.
Measured: 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 treatment arm (droxidopa and placebo) compared to baseline.
Measured: 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 placebo and droxidopa treatment arms
Measured: 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
Measured: 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 Time standing duration
Measured: Change from baseline in standing time duration during each 6 week treatment arm (droxidopa and placebo).
Change From Baseline in Timed Up and Go (TUG) Test Performance
Change from baseline in Timed Up and Go (TUG) test performance
Measured: Change from baseline in TUG test performance during each 6 week treatment arm (droxidopa and placebo)
Change From Baseline in 6 Minute Walk Test Performance
Change from baseline in 6 minute walk test performance
Measured: Change from baseline in the 6MW distance during each 6 week treatment arm (droxidopa and placebo)
Change From Baseline in Scores on the Orthostatic Hypotension Symptom Assessment (OHSA) Questionnaire
Change from baseline in scores on the Orthostatic Hypotension Symptom Assessment questionnaire. The scale rates the severity of OH symptoms from 0 to 10 ; with 10 defined as the worst possible.
Measured: Change from baseline in OHSA score during each 6 week treatment arm (droxidopa and placebo)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2021
- Study start12 Jul 2021
- Primary completion30 Oct 2023
- Study completion29 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Menkes DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind Placebo-controlled Randomized Crossover Clinical Trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stephen G. Kaler, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Stephen G. Kaler, MD, Nationwide Children's Hospital
- Investigators
- Stephen G Kaler, MD, Principal investigator, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04977388
- Sponsor's protocol ID
- 00001113
- Status last verified
- Mar 2026
- First submitted
- 9 Jul 2021
- Last updated
- 13 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kaler MM, Brock G, Jeanty CJ, Iammarino MA, Hampton KA, Pham MT, Sabo BT, Lowes LP, Sullivan P, Goldstein DS, Kaler SG. Safety and efficacy of droxidopa for dysautonomia in adults with Menkes disease and occipital horn syndrome in the USA: a randomised phase 1/2a crossover trial. EClinicalMedicine. 2026 Apr 13;94:103898. doi: 10.1016/j.eclinm.2026.103898. eCollection 2026 Apr.
PubMed 42016919
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04977388
- Acronym / sponsor ID
- 00001113
- Conditions
- Menkes Disease, Occipital Horn Syndrome
- Keywords
- Dysautonomia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Stephen G. Kaler, MDUniversity, hospital or other
- Study start
- 12 Jul 2021 (actual)
- Primary completion
- 30 Oct 2023 (actual)
- Study completion
- 29 Jun 2024 (actual)
- First posted
- 26 Jul 2021 (actual)
- Results
- Posted 13 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-blind Placebo-controlled Randomized Crossover Clinical Trial
| Arm | Type | Receives |
|---|---|---|
| Northera™ (Droxidopa) (Treatment A) | Active comparator | Drug: DroxidopaNorthera (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. |
| Placebo (Treatment B) | Placebo comparator | Other: PlaceboEmpty 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 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DroxidopaAlso: NortheraSubjects will self-administer capsules of Droxidopa by mouth twice daily for six weeks. | Drug | Northera™ (Droxidopa) (Treatment A) |
| PlaceboSubjects will self-administer capsules of placebo by mouth twice daily for six weeks. | Other | Placebo (Treatment B) |
Primary outcome
Treatment Related Adverse Events as Assessed by CTCAE v4.0
Time frame: TEAEs in 6 week periods of either active drug (droxidopa) or placebo
Treatment related adverse events as assessed by CTCAE v 4.0 by study arm
8 secondary outcomes
Mean Change in Systolic Blood Pressure in Tilt Position
Time frame: 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
Time frame: The change in diastolic BP in tilt position during each 6 week treatment arm (droxidopa and placebo) compared to baseline.
Plasma Catechol Levels
Time frame: Change in plasma catechols between each 6 week treatment arm (droxidopa and placebo)
Change From Baseline in Daily Bowel Movements
Time frame: 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
Time frame: Change from baseline in standing time duration during each 6 week treatment arm (droxidopa and placebo).
Change From Baseline in Timed Up and Go (TUG) Test Performance
Time frame: Change from baseline in TUG test performance during each 6 week treatment arm (droxidopa and placebo)
Change From Baseline in 6 Minute Walk Test Performance
Time frame: Change from baseline in the 6MW distance during each 6 week treatment arm (droxidopa and placebo)
Change From Baseline in Scores on the Orthostatic Hypotension Symptom Assessment (OHSA) Questionnaire
Time frame: Change from baseline in OHSA score during each 6 week treatment arm (droxidopa and placebo)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42016919Kaler MM, Brock G, Jeanty CJ, Iammarino MA, Hampton KA, Pham MT, Sabo BT, Lowes LP, Sullivan P, Goldstein DS, Kaler SG. Safety and efficacy of droxidopa for dysautonomia in adults with Menkes disease and occipital horn syndrome in the USA: a randomised phase 1/2a crossover trial. EClinicalMedicine. 2026 Apr 13;94:103898. doi: 10.1016/j.eclinm.2026.103898. eCollection 2026 Apr.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen G Kaler, MD principal investigator
Vagelos College of Physicians & Surgeons, Columbia University, New York, NY
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Droxidopa in people with Menkes Disease and Occipital Horn Syndrome, run by Stephen G. Kaler, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Related Adverse Events as Assessed by CTCAE v4.0 (time frame: TEAEs in 6 week periods of either active drug (droxidopa) or placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04977388, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.