Menkes DiseasePhase 3NCT00811785
Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency
A Phase 3 study testing Copper Histidine in people with Menkes Disease and Occipital Horn Syndrome, run by Cyprium Therapeutics, Inc. at 1 site in United States.
Trial summary
Menkes disease and occipital horn syndrome are two forms of copper deficiency that must be diagnosed and treated very early in life to prevent serious developmental problems. However, these and other forms of copper deficiency are not very well understood, and further research is needed to determine whether certain… Read more about this study
- Who is it for?
- Ages Up to 80 years
- Conditions the study is for
- Menkes Disease, Occipital Horn Syndrome, Unexplained Copper Deficiency
- What is being tested?
- Copper Histidine
- Type of treatment
- Injection or infusion
- How many people
- 93 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2009to 28 Aug 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 Up to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form by parent or legal guardian, or the subject himself/herself.
- Male or female, aged 0 to 80 years.
- Diagnosed with classic Menkes disease, Occipital Horn Syndrome (OHS), or unexplained copper deficiency.
- Serum copper level results between 0 and 75 mg/dl (normal range 80-180 microgram/dl).
- Ability to adhere to the prescribed subcutaneous Copper Histidinate injection regimen.
- Willingness to comply with all study visits and procedures.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pre-existing liver (e.g., hepatitis, biliary atresia, cirrhosis) or kidney disease (e.g., serum creatinine >1.0 mg/dL)
- History of bleeding diatheses
- Pregnancy or lactation
- Diagnosis of Wilson disease
- Any disease or condition that, in the opinion of the Investigator, has a high probability of precluding the patient from completing the study or where the patient cannot or will not appropriately comply with study requirements
Show all 16Show fewer
- Participation in any other investigational trial in which receipt of investigational drug or device occurred within 30 days prior to screening for this study
- History of diagnosed drug or alcohol dependence within the previous 3 years
- Any disease process that may adversely affect gastrointestinal absorption, e.g. celiac sprue
- Chronic/severe cardiac disease (applies to adult subjects only) that could make participating in a clinical trial physically demanding, including but not limited to cardiac insufficiency, arrhythmias, bradycardia, or hypotension, unless associated with other features of dysautonomia, as in OHS.
- History of cerebrovascular accident (applies to adult subjects only) that could make participating in a clinical trial difficult for the subject.
- Adults who are, or who may be, unable to consent will not be allowed to participate in this study. This is because we did not encounter subjects in this category for whom enrollment would be necessary or appropriate in our previous studies (90-CH-0149, 90-N-0149) with this IND. The main populations to be recruited are 1) pediatric subjects under 18 years of age with inherited copper transport disorders, and 2) non-cognitively-impaired adults with unexplained copper deficiency.
- NIH employees are eligible to participate in this protocol if they meet the Inclusion criteria and have no exclusion criteria. Recruitment, enrollment and compensation of NIH employee subjects will be consistent with the Guidelines for the Inclusion of Employees in NIH Intramural Research Studies (December 2015) and NIH Policy Manual Chapter 2300-630-3, "Leave Policy for NIH Employees Participating in NIH Medical Research Studies". The consenting research team member will make the NIH Information Sheet on Employee Research Participation available to staff members who are considering enrolling.
- If the individual requesting to participate in the protocol is a co-worker, the consent from the NIH staff member (co-worker) will not be obtained by the staff member s direct supervisor but by another research staff member approved for obtaining informed consent who is not a co-worker.
- Neither participation nor refusal to participate as a subject in this protocol will have an effect, either beneficial or adverse, on the participant s employment or position at NIH.
- Employee subjects' privacy and confidentiality will be respected by protocol and consenting staff the same as for all subjects participating in research protocols. However, all subjects will be made aware that there are limits to these protections.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Menkes disease and occipital horn syndrome are two forms of copper deficiency that must be diagnosed and treated very early in life to prevent serious developmental problems. However, these and other forms of copper deficiency are not very well understood, and further research is needed to determine whether certain treatments are useful in treating copper deficiency. One such treatment is copper histidine, a copper replacement that can be injected directly into the body to avoid absorption through the gastrointestinal tract. This study will investigate the effectiveness, side effects, and dosage of copper histidine treatment for patients with copper deficiency. It will also collect medical history information from patients to allow researchers to study possible genetic and nongenetic origins of copper deficiency.
This study will include 100 subjects, all of whom will be children and adults who have been diagnosed with Menkes disease, occipital horn syndrome, or other unexplained copper deficiency.
Read more
Patients will receive a prescribed dose of copper histidine, which will be administered daily as an injection.
During the study, patients will be admitted to the NIH Clinical Center on an outpatient basis to evaluate their response to the copper histidine treatment. These evaluations will take place every 8 months, with a final evaluation performed after 3 years of treatment. During the outpatient visits, patients will be required to give blood and urine samples for testing and undergo ultrasound testing. They will also undergo brain MRI scans at the initial visit and at the 16-month and 36-month visits. Patients who agree will give additional blood samples for genetic research purposes.
Read the detailed description
Study Description:
The purpose of this study is to allow currently enrolled participants to complete their three-year course of subcutaneous Copper Histidinate treatment under the protocol. We hypothesize that subcutaneous injections of this drug will raise serum copper levels and ceruloplasmin levels in enrolled participants, improve neurodevelopmental and neurological outcomes, and reduce mortality compared to untreated affected subjects.
Objectives:
-Primary Objective: Evaluate responses to Copper Histidinate treatment for clinical care.
Endpoints:
-Completion of three years treatment by 13 remaining subjects
Study Population:
The 13 remaining subjects
Phase: Clinical Care/Treatment only
Description of Sites/Facilities Enrolling Participants: The study will occur at the NIH Clinical Center
Description of Study Intervention:
The study intervention is administration of Copper Histidinate in dose(s) prescribed as follows: 250 microgram sc b.i.d. in infants up to 12 months of age, and 250 microgram sc q.d. for infants and children older than 12 months. The total duration of copper histidinate treatment will not exceed three years.
Study Duration:
The estimated time from when the study opens to enrollment until completion is approximately 151 months (02/27/2009-09/30/2021). (May end sooner pending FDA new drug approval.)
Participant Duration:
The time it will take for each individual participant to complete all participant visits is approximately 36 months. There are 13 subjects with a total of 31 visits to complete.
- Being tested
- Copper Histidine
- Keywords
- Copper Deficiency, Menkes Disease, Neurodegeneration, Occipital Horn Syndrome, Copper
- Medical subject headings
- Menkes Kinky Hair Syndrome, Occipital horn syndrome, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Copper HistidineDrug
Daily subcutaneous injections for three years
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess neurological improvement in patients with OHS or unexplained copper deficiency treated with subcutaneous CuHis injections.
Neurological Improvement: reduction in dysautonomia symptoms in OHS, and improved nerve conduction tests in unexplained copper deficiency
Measured: Three years
Secondary outcomes (1)
To assess survival in classic Menkes disease subjects treated with subcutaneous CuHis injections in comparison with classic Menkes patients who did not receive any type of copper treatment.
Under-three Mortality. This endpoint will be assessed continuously
Measured: Continuously
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2008 (estimated)
- Study start27 Feb 2009
- Primary completion28 Aug 2020
- Study completion28 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cyprium Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00811785
- Sponsor's protocol ID
- 090059
- Other IDs
- 09-CH-0059
- Status last verified
- Aug 2019
- First submitted
- 18 Dec 2008
- Last updated
- 19 Nov 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kaler SG, Goldstein DS, Holmes C, Salerno JA, Gahl WA. Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease. Ann Neurol. 1993 Feb;33(2):171-5. doi: 10.1002/ana.410330206.
PubMed 8434878Kaler SG, Westman JA, Bernes SM, Elsayed AM, Bowe CM, Freeman KL, Wu CD, Wallach MT. Gastrointestinal hemorrhage associated with gastric polyps in Menkes disease. J Pediatr. 1993 Jan;122(1):93-5. doi: 10.1016/s0022-3476(05)83496-1.
PubMed 8419622Kaler SG, Gahl WA, Berry SA, Holmes CS, Goldstein DS. Predictive value of plasma catecholamine levels in neonatal detection of Menkes disease. J Inherit Metab Dis. 1993;16(5):907-8. doi: 10.1007/BF00714295. No abstract available.
PubMed 8295415
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency
- ClinicalTrials.gov ID
- NCT00811785
- Acronym / sponsor ID
- 090059
- Keywords
- Copper Deficiency, Menkes Disease, Neurodegeneration, Occipital Horn Syndrome, Copper
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Cyprium Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 27 Feb 2009
- Primary completion
- 28 Aug 2020 (actual)
- Study completion
- 28 Aug 2020 (actual)
- First posted
- 19 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Menkes disease and occipital horn syndrome are two forms of copper deficiency that must be diagnosed and treated very early in life to prevent serious developmental problems. However, these and other forms of copper deficiency are not very well understood, and further research is needed to determine whether certain treatments are useful in treating copper deficiency. One such treatment is copper histidine, a copper replacement that can be injected directly into the body to avoid absorption through the gastrointestinal tract. This study will investigate the effectiveness, side effects, and dosage of copper histidine treatment for patients with copper deficiency. It will also collect medical history information from patients to allow researchers to study possible genetic and nongenetic origins of copper deficiency.
This study will include 100 subjects, all of whom will be children and adults who have been diagnosed with Menkes disease, occipital horn syndrome, or other unexplained copper deficiency.
Patients will receive a prescribed dose of copper histidine, which will be administered daily as an injection.
During the study, patients will be admitted to the NIH Clinical Center on an outpatient basis to evaluate their response to the copper histidine treatment. These evaluations will take place every 8 months, with a final evaluation performed after 3 years of treatment. During the outpatient visits, patients will be required to give blood and urine samples for testing and undergo ultrasound testing. They will also undergo brain MRI scans at the initial visit and at the 16-month and 36-month visits. Patients who agree will give additional blood samples for genetic research purposes.
Detailed description
Study Description:
The purpose of this study is to allow currently enrolled participants to complete their three-year course of subcutaneous Copper Histidinate treatment under the protocol. We hypothesize that subcutaneous injections of this drug will raise serum copper levels and ceruloplasmin levels in enrolled participants, improve neurodevelopmental and neurological outcomes, and reduce mortality compared to untreated affected subjects.
Objectives:
-Primary Objective: Evaluate responses to Copper Histidinate treatment for clinical care.
Endpoints:
-Completion of three years treatment by 13 remaining subjects
Study Population:
The 13 remaining subjects
Phase: Clinical Care/Treatment only
Description of Sites/Facilities Enrolling Participants: The study will occur at the NIH Clinical Center
Description of Study Intervention:
The study intervention is administration of Copper Histidinate in dose(s) prescribed as follows: 250 microgram sc b.i.d. in infants up to 12 months of age, and 250 microgram sc q.d. for infants and children older than 12 months. The total duration of copper histidinate treatment will not exceed three years.
Study Duration:
The estimated time from when the study opens to enrollment until completion is approximately 151 months (02/27/2009-09/30/2021). (May end sooner pending FDA new drug approval.)
Participant Duration:
The time it will take for each individual participant to complete all participant visits is approximately 36 months. There are 13 subjects with a total of 31 visits to complete.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form by parent or legal guardian, or the subject himself/herself.
- Male or female, aged 0 to 80 years.
- Diagnosed with classic Menkes disease, Occipital Horn Syndrome (OHS), or unexplained copper deficiency.
- Serum copper level results between 0 and 75 mg/dl (normal range 80-180 microgram/dl).
Key exclusion criteria (16 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pre-existing liver (e.g., hepatitis, biliary atresia, cirrhosis) or kidney disease (e.g., serum creatinine >1.0 mg/dL)
- History of bleeding diatheses
- Pregnancy or lactation
- Diagnosis of Wilson disease
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 |
|---|---|---|
| Copper HistidineDaily subcutaneous injections for three years | Drug | – |
Primary outcome
To assess neurological improvement in patients with OHS or unexplained copper deficiency treated with subcutaneous CuHis injections.
Time frame: Three years
Neurological Improvement: reduction in dysautonomia symptoms in OHS, and improved nerve conduction tests in unexplained copper deficiency
1 secondary outcome
To assess survival in classic Menkes disease subjects treated with subcutaneous CuHis injections in comparison with classic Menkes patients who did not receive any type of copper treatment.
Time frame: Continuously
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2020.
- Background: PubMed 8434878Kaler SG, Goldstein DS, Holmes C, Salerno JA, Gahl WA. Plasma and cerebrospinal fluid neurochemical pattern in Menkes disease. Ann Neurol. 1993 Feb;33(2):171-5. doi: 10.1002/ana.410330206.
- Background: PubMed 8419622Kaler SG, Westman JA, Bernes SM, Elsayed AM, Bowe CM, Freeman KL, Wu CD, Wallach MT. Gastrointestinal hemorrhage associated with gastric polyps in Menkes disease. J Pediatr. 1993 Jan;122(1):93-5. doi: 10.1016/s0022-3476(05)83496-1.
- Background: PubMed 8295415Kaler SG, Gahl WA, Berry SA, Holmes CS, Goldstein DS. Predictive value of plasma catecholamine levels in neonatal detection of Menkes disease. J Inherit Metab Dis. 1993;16(5):907-8. doi: 10.1007/BF00714295. No abstract available.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Copper Histidine in people with Menkes Disease and Occipital Horn Syndrome, run by Cyprium Therapeutics, Inc. 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 16 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 19 Nov 2020. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To assess neurological improvement in patients with OHS or unexplained copper deficiency treated with subcutaneous CuHis injections. (time frame: Three years). 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 NCT00811785, which also lists 3 linked publications.
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 19 Nov 2020.