GTA-Glyceryltriacetate for Canavan Disease

• ClinicalTrials.gov Identifier: NCT00278707
• Recruitment Status: Unknown
• First Posted: January 18, 2006
• Last Update Posted: August 15, 2006
• Sponsor: Sheba Medical Center
• Information provided by: Sheba Medical Center

Tracking Information

• First Submitted Date: January 15, 2006
• First Posted Date: January 18, 2006
• Last Update Posted Date: August 15, 2006
• Study Start Date: January 2006
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: January 15, 2006)

• All primary outcome will be evaluated 4 months following the initiation of treatment:
• Neurological Status
• Brain Imaging: MRI & MRS
• NAA Levels in Urine
• Ophthalmologic Examination

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: GTA-Glyceryltriacetate for Canavan Disease
• Official Title: Phase 1 Treatment With GTA in Two Infant With Canavan Disease
• Brief Summary: The purpose of this study is to determine whether oral supplementation of glyceryl triacetate improves the clinical prognosis of Canavan Disease.

Detailed Description

Canavan Disease is caused by a deficiency in the enzyme named Aspartoacylase (ASPA). This disease is a devastating, progressive disease with no available treatment. As a result of the ASPA deficiency, there are high levels of N-acetylaspartate (NAA) and low levels of L-aspartate and acetate.

We hypothesize that one of the functions of ASPA is to provide sufficient levels of acetate for CNS myelinization. For this reason, we offer to supplement acetate levels by the oral administration of glyceryl triacetate (GTA). Such treatment must be offered to patients before the age of 18 months, prior to the termination of CNS myelinization.

1. Two patients, aged less than 15 months, will receive daily doses of oral GTA
2. The daily dose will be increased incrementally until the maintenance dose is reached. This will be done under close monitoring of the patients, including periodic blood gas sampling.
3. GTA has not been shown to cause any known toxicity, according to the Cosmetic Ingredient Review Expert Panel (Fiume, 2003).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Infantile Canavan Disease
• Deficiency Disease, Aspartoacylase

• Intervention: Drug: GTA: Glyceryltriacetate
• Study Arms: Not Provided

Publications *

• Mathew R, Arun P, Madhavarao CN, Moffett JR, Namboodiri MA. Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain. J Pharmacol Exp Ther. 2005 Oct;315(1):297-303. doi: 10.1124/jpet.105.087536. Epub 2005 Jul 7.
• Madhavarao CN, Arun P, Moffett JR, Szucs S, Surendran S, Matalon R, Garbern J, Hristova D, Johnson A, Jiang W, Namboodiri MA. Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5221-6. doi: 10.1073/pnas.0409184102. Epub 2005 Mar 22.

Recruitment Information

• Recruitment Status: Unknown status
• Enrollment (submitted: January 15, 2006): 5
• Original Enrollment: Same as current
• Study Completion Date: July 2006
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

• Age below 15 months
• Biochemically diagnosed with Canavan Disease

Exclusion Criteria:

• None

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Years to 15 Months (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT00278707
• Other Study ID Numbers: SHEBA-05-3968-YA-CTIL
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Sheba Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Yair Anikster, MD PI; Director Metabolic Disease Unit

• PRS Account: Sheba Medical Center
• Verification Date: August 2006