Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency | oneedsvoice

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Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency

study id #: NCT00811785

condition: Menkes Disease, Occipital Horn Syndrome

status: active, not recruiting


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.

intervention: Copper Histidine

start date: February 27, 2009

estimated completion: September 30, 2021

last updated: December 17, 2018

phase of development: Phase 3

size / enrollment: 93

study description: Menkes is a fatal genetic form of copper deficiency caused by mutations in a copper-transporting ATPase (ATP7A). Pre-symptomatic diagnosis and therapy with copper injections is associated with improved overall survival and, based on their molecular defects, with vastly better neurological outcomes in some patients compared to the usual natural history. One purpose of this study is to further evaluate the relationship between specific molecular defects and clinical responses to early copper treatment in Menkes disease. In addition, we seek to study the influence of parenteral copper treatment in related genetic disorders, and in unexplained copper deficiency conditions, often associated with non-specific neurological abnormalities.

primary outcomes:

  • Neurodevelopment [ Time Frame:Three years ]
    Study drug toxicity

secondary outcomes:

  • Survival [ Time Frame:Three years ]

inclusion criteria: -Serum copper levels less than 75 micrograms/dl

exclusion criteria: - pre-existing liver or kidney disease
- history of bleeding diatheses
- pregnancy
- 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
- 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
- disease processes that may adversely affect gastrointestinal absorption
- chronic/severe cardiac disease including but not limited to cardiac insufficiency, arrhythmias, bradycardia, or hypotension, or a history of cerebrovascular accident (CVA).

sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

investigators: Stephen G Kaler, M.D.

locations: United States