Homocystinuria: Treatment With N-Acetylcysteine

Homocystinuria Clinical Trial

Official title:

Homocystinuria: Treatment With N-Acetylcysteine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00483314
• Other study ID #: #6-FY06-317
• Status: Completed
• Phase: Phase 2
• First received: June 5, 2007
• Last updated: February 16, 2009
• Start date: November 2007
• Est. completion date: February 2009

Study information

• Verified date: February 2009
• Source: McGill University Health Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

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:

1. 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.

2. Measurement of flow-mediated vasodilation of the brachial artery (endothelial function) in response to NAC treatment. Endothelial dysfunction is a precursor of atherogenesis.

3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: February 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Homocystinuria

Intervention

Drug:
• N-acetylcysteine
2 g p.o. BID x 60 days

Locations

Country	Name	City	State
Canada	MUHC-Royal Victoria Hospital	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
McGill University Health Center	March of Dimes

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lowering plasma total homocysteine		3 months	No
Secondary	Change in flow-mediated dilatation of brachial artery		3 months	No

External Links

•   funding agency