Homocystinuria: Treatment With N-Acetylcysteine - Full Text View

Sponsor:	McGill University Health Center
Collaborator:	March of Dimes
Information provided by:	McGill University Health Center
ClinicalTrials.gov Identifier:	NCT00483314

Purpose

The purpose of this study is determine if oral N-acetylcysteine is effective in lowering homocysteine in individuals with homocystinuria.

Condition	Intervention	Phase
Homocystinuria	Drug: N-acetylcysteine	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Homocystinuria: Treatment With N-Acetylcysteine

Resource links provided by NLM:

Genetics Home Reference related topics: argininosuccinic aciduria citrullinemia homocystinuria N-acetylglutamate synthase deficiency ornithine translocase deficiency succinic semialdehyde dehydrogenase deficiency

Drug Information available for: Acetylcysteine

U.S. FDA Resources

Further study details as provided by McGill University Health Center:

Primary Outcome Measures:

Lowering plasma total homocysteine [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in flow-mediated dilatation of brachial artery [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment:	5
Study Start Date:	November 2007
Study Completion Date:	February 2009
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: N-acetylcysteine 2 g p.o. BID x 60 days

Detailed Description:

Homocystinuria (MIM 236200) due to CBS deficiency is the most common inborn error of sulfur amino acid metabolism with severe clinical manifestations. We propose:

An open-label pilot study of N-acetylcysteine (NAC) to lower plasma homocysteine levels in those that have not responded to conventional treatment which includes betaine (Cystadane®, Orphan Medical Inc.), which while lowering Hcy levels does not normalize it, and is very expensive. There are no known contraindications to NAC used for nutritional supplementation and it is relatively inexpensive.

Oral NAC has reduced total plasma homocysteine in healthy subjects in a dose-dependent fashion.
Measurement of flow-mediated vasodilation of the brachial artery (endothelial function) in response to NAC treatment. Endothelial dysfunction is a precursor of atherogenesis.
Sequencing the CBS gene in these individuals in order to identify novel mutations causing homocystinuria and identify polymorphisms in other genes that may affect response to treatment.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Homocystinuria (lens dislocation and hyperhomocysteinemia)
Age ≥ 18 (the age of majority in Canada)

Exclusion Criteria:

Nursing mothers or pregnant women
Chronic liver disease
Taking nitrates
Cystine stone formers
History of active peptic ulcer disease
Subjects receiving carbamazepine and metoclopramide
Use of other products containing cysteine or N-acetylcysteine (e.g. nebulized NAC, cysteine supplements, methionine restriction)
Hypersensitivity to any ingredient in the study product
Clinically significant, abnormal laboratory test on screening (Visit 2)

Other Criteria:

Women of child-bearing capacity must be using an acceptable method of birth control and have a negative pregnancy test before being enrolled

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00483314

Locations

Canada, Quebec
Royal Victoria Hospital
Montreal, Quebec, Canada, H3A 1A1
MUHC-Royal Victoria Hospital
Montreal, Quebec, Canada, H3A 1A1

Sponsors and Collaborators

McGill University Health Center

March of Dimes

Investigators

Principal Investigator:

Brian M GILFIX, MD, PhD

McGill University Health Center

More Information

Additional Information:

funding agency This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	McGill University Health Centre ( Brian M. Gilfix, Principal Investigator )
Study ID Numbers:	#6-FY06-317
Study First Received:	June 5, 2007
Last Updated:	February 16, 2009
ClinicalTrials.gov Identifier:	NCT00483314 History of Changes
Health Authority:	Canada: Health Canada

Additional relevant MeSH terms:

Respiratory System Agents
Anti-Infective Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Brain Diseases
Metabolism, Inborn Errors
Therapeutic Uses
Free Radical Scavengers
Connective Tissue Diseases
Acetylcysteine
Brain Diseases, Metabolic, Inborn
Antidotes

Metabolic Diseases
Amino Acid Metabolism, Inborn Errors
Nervous System Diseases
Central Nervous System Diseases
Homocystinuria
Antiviral Agents
Protective Agents
Pharmacologic Actions
Genetic Diseases, Inborn
Expectorants
N-monoacetylcystine
Brain Diseases, Metabolic

ClinicalTrials.gov processed this record on November 30, 2009