Copper Histidine Therapy for Menkes Diseases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier:
NCT00001262
First received: November 3, 1999
Last updated: July 11, 2013
Last verified: January 2012
  Purpose

Menkes Disease is a genetic disorder affecting the metabolism of copper. Patient with this disease are both physically and mentally retarded. Menkes disease is usually first detected in the first 2-3 months of life. Infant males born with the disease fail to thrive, experience hypothermia, have delayed development, and experience seizures. These infants also have characteristic physical features such as changes of their hair and face. Females may also have changes in hair and skin color, but rarely have significant medical problems.

Appropriate treatment of Menkes Disease requires that the disease be diagnosed early and treatment started before irreversible brain damage occurs. The aim of treatment is to bypass the normal route of absorption of copper through the gastrointestinal tract. Copper must then be delivered to brain cells and be available for use by enzymes.

Copper histidine is a copper replacement that can be injected directly into the body to avoid absorption through the gastrointestinal tract. However, studies have shown the genetic abnormalities causing Menkes disease cannot simply be corrected by copper replacement injections.

The genetic abnormality causing Menkes disease can vary in its severity. Patients with a genetic abnormality that may still permit some production of the enzymes required to process copper may receive benefit from early treatment with copper replacement. However, patients with severe abnormalities of the genes responsible for copper metabolism may receive no benefit from copper replacement.

The purpose of this study is to continue to evaluate the effects of early copper histidine in Menkes disease patients and to correlate specific molecular defects with responses to treatment.


Condition Intervention Phase
Kinky Hair Syndrome
Drug: Copper Histidine
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Early Copper Histidine Therapy in Menkes Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Clinical neurodevelopment. [ Time Frame: Up to age three years ] [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: June 1990
Study Completion Date: July 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Copper Histidine
    N/A
Detailed Description:

Menkes disease is an X-linked recessive neurodegenerative disorder caused by defects in a gene that encodes an evolutionarily conserved copper-transporting ATPase (ATP7A). Several issues must be addressed in configuring therapeutic strategies for this disorder: (a) affected infants must be identified and treatment commenced very early in life before irreparable neurodegeneration occurs, (b) the block in intestinal absorption of copper must be bypassed, (c) circulating copper must be delivered to the brain, and (d) copper must be available to enzymes within cells that require it as a cofactor.

Very early, pre-symptomatic therapy with copper injections has been associated with improved overall survival and, in some patients - based on their molecular defects, with vastly better neurological outcomes in comparison to the usual natural history of this disorder. The purpose of this study is to continue to provide early copper treatment to other newborn infants diagnosed as having Menkes disease. We have established that three years duration of treatment is adequate for prevention of neurodegeneration in this disorder.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Newborn infants in whom Menkes disease is confirmed on biochemical or molecular grounds and in whom no neurological symptoms are present are eligible for enrollment in this study.

EXCLUSION CRITERIA:

Newly identified patients classified as symptomatic at the time of diagnosis, and affected individuals with mild phenotypes are not currently eligible for this clinical trial.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00001262

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen G Kaler, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT00001262     History of Changes
Other Study ID Numbers: 900149, 90-CH-0149
Study First Received: November 3, 1999
Last Updated: July 11, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Menkes
Copper
X-Linked
Neurogeneration

Additional relevant MeSH terms:
Menkes Kinky Hair Syndrome
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors
Hair Diseases
Skin Diseases
Metabolic Diseases
Copper
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014