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: September 29, 2015
Last verified: September 2015

November 3, 1999
September 29, 2015
June 1990
July 2012   (final data collection date for primary outcome measure)
  • Gross Motor Development at 36 Mos of Age or at Death (Mos) [ Time Frame: 36 months or death ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
Not Provided
Complete list of historical versions of study NCT00001262 on ClinicalTrials.gov Archive Site
  • Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Weight Percentile [ Time Frame: 36 months or death ] [ Designated as safety issue: No ]
  • Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Length Percentile [ Time Frame: 36 months or death ] [ Designated as safety issue: No ]
  • Somatic Growth Percentiles at 3 Years of Age (or at Age of Death) - Head Circumference Percentile [ Time Frame: 36 months or death ] [ Designated as safety issue: No ]
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Copper Histidine Therapy for Menkes Diseases
Early Copper Histidine Therapy in Menkes Disease

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.

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Kinky Hair Syndrome
Drug: Copper Histidine
Experimental: Copper histidine
Intervention: Drug: Copper Histidine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
July 2013
July 2012   (final data collection date for primary outcome measure)
  • 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.

Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00001262
900149, 90-CH-0149
Yes
Not Provided
Not Provided
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Principal Investigator: Stephen G Kaler, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health Clinical Center (CC)
September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP