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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by National Institutes of Health Clinical Center (CC)
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ) Identifier:
First received: December 18, 2008
Last updated: May 21, 2016
Last verified: May 2016

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.

Condition Intervention Phase
Menkes Disease
Occipital Horn Syndrome
Drug: Copper Histidine
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Molecular Bases of Response to Copper Treatment in Menkes Disease, Related Phenotypes, and Unexplained Copper Deficiency

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Neurodevelopment, or neurological improvement [ Time Frame: Three years ] [ Designated as safety issue: Yes ]
    Study drug toxicity

Secondary Outcome Measures:
  • Survival [ Time Frame: Three years ]

Estimated Enrollment: 100
Study Start Date: December 2008
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Copper Histidine
    A physiologically acceptable form of the trace metal copper.
Detailed 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.

Ages Eligible for Study:   up to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Serum copper levels less than 75 micrograms/dl


  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00811785

Contact: Stephen G Kaler, M.D. (301) 451-6034

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Complementary and Integrative Health (NCCIH)
Principal Investigator: Stephen G Kaler, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Identifier: NCT00811785     History of Changes
Other Study ID Numbers: 090059  09-CH-0059 
Study First Received: December 18, 2008
Last Updated: May 21, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Copper Deficiency
Menkes Disease
Occipital Horn Syndrome

Additional relevant MeSH terms:
Menkes Kinky Hair Syndrome
Cutis Laxa
Ehlers-Danlos Syndrome
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Cardiovascular Diseases
Central Nervous System Diseases
Collagen Diseases
Congenital Abnormalities
Connective Tissue Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hair Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Heredodegenerative Disorders, Nervous System
Intellectual Disability
Mental Retardation, X-Linked
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors
Nervous System Diseases
Neurobehavioral Manifestations
Neurologic Manifestations
Skin Abnormalities
Skin Diseases
Skin Diseases, Genetic
Vascular Diseases processed this record on May 25, 2016