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Trial record 2 of 2 for:    Menkes disease + NICHD

Copper Histidine Therapy for Menkes Diseases

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00001262
First Posted: November 4, 1999
Last Update Posted: October 30, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
  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 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
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) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):

Primary Outcome Measures:
  • Gross Motor Development at 36 Mos of Age or at Death (Mos) [ Time Frame: 36 months or death ]
    This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate gross motor development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age.

  • Fine Motor Adaptive Development at 36 Mos of Age or at Death (Mos) [ Time Frame: 36 months or death ]
    This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate fine motor development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age.

  • Personal-Social Development at 36 Mos of Age or at Death (Mos) [ Time Frame: 36 months or death ]
    This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate personal-social development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age.

  • Language Development at 36 Mos of Age or at Death (Mos) [ Time Frame: 36 months or death ]
    This was measured based on the Denver Developmental Screening Test (DDST) I or II for age-appropriate language development in apparently normal healthy subjects at specific ages (in months). The DDST employs a grid to assess expected developmental milestones in relation to chronologic age.


Secondary Outcome Measures:
  • Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Weight Percentile [ Time Frame: 36 months or death ]
  • Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Length Percentile [ Time Frame: 36 months or death ]
  • Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Head Circumference Percentile [ Time Frame: 36 months or death ]

Enrollment: 60
Study Start Date: June 1990
Study Completion Date: July 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Copper histidine Drug: Copper Histidine

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001262


Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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:

Responsible Party: 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
First Submitted: November 3, 1999
First Posted: November 4, 1999
Results First Submitted: August 5, 2014
Results First Posted: October 30, 2015
Last Update Posted: October 30, 2015
Last Verified: September 2015

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
Menkes
Copper
X-Linked
Neurodegeneration
ATP7A

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