Muscular Dystrophies Clinical Trial
Official title:
Phase I Gene Transfer of rAAV1.tMCK.Human-alpha-sarcoglycan for Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)
Limb girdle muscular dystrophy type 2D (LGMD2D) is a genetic disease that affects skeletal muscle. Insufficient levels of the protein alpha-sarcoglycan result in muscle weakness that worsens over time. The purpose of this study is to evaluate the safety and effectiveness of gene therapy in treating children and adults with LGMD2D.
Status | Completed |
Enrollment | 6 |
Est. completion date | August 2011 |
Est. primary completion date | June 2011 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 5 Years and older |
Eligibility |
Inclusion Criteria: - Six LGMD2D subjects ages 5 and older based on the clinical degree of involvement (impaired muscle function/weakness, sufficient muscle preservation) - Preservation of EDB muscle or another muscle if judged more favorable because of adequate muscle mass for gene transfer - Males and females of any ethnic group - Established mutations of an -SG gene on both alleles - Ability to cooperate for testing - Sexually active patients must be willing to practice a reliable method of contraception during the study Exclusion Criteria: - Active viral infection (symptoms listed in section 9.0 of the protocol) - LGMD2D subjects without weakness or functional loss - Cardiomyopathy based on clinical exam and ECHO with ejection fraction less than 40% - HIV infected - Hepatitis A, B, or C infected - Autoimmune diseases and immunosuppressive drugs (other than pulse methylprednisolone at time of gene transfer) - Persistent leucopenia or leucocytosis (WBC less than or equal to 3.5 K/cu mm or at least 20.0 K/ cu mm) or neutrophils less than 1.5 K/ cu mm - Concomitant illness or requirement for chronic drug treatment that in the opinion of the Principal Investigator creates unnecessary risks for gene transfer - Pregnancy - Abnormal laboratory values considered clinically significant - Alcoholism (CAGE questionnaire), and laboratory tests such as GGT and MCV |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | The Research Institute at Nationwide Children's Hospital | Columbus | Ohio |
Lead Sponsor | Collaborator |
---|---|
Nationwide Children's Hospital | Muscular Dystrophy Association, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
United States,
Allamand V, Donahue KM, Straub V, Davisson RL, Davidson BL, Campbell KP. Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice. Gene Ther. 2000 Aug;7(16):1385-91. — View Citation
Bueno MR, Moreira ES, Vainzof M, Chamberlain J, Marie SK, Pereira L, Akiyama J, Roberds SL, Campbell KP, Zatz M. A common missense mutation in the adhalin gene in three unrelated Brazilian families with a relatively mild form of autosomal recessive limb-girdle muscular dystrophy. Hum Mol Genet. 1995 Jul;4(7):1163-7. — View Citation
Büning H, Nicklin SA, Perabo L, Hallek M, Baker AH. AAV-based gene transfer. Curr Opin Mol Ther. 2003 Aug;5(4):367-75. Review. — View Citation
Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR. Sustained alpha-sarcogly — View Citation
Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR. Limb-girdle muscular dystrophy type 2D gene the — View Citation
Rodino-Klapac LR, Lee JS, Mulligan RC, Clark KR, Mendell JR. Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D. Neurology. 2008 Jul 22;71(4):240-7. doi: 10.1212/01.wnl.0000306309.85301.e2. Epub 2008 Jun 4. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety of AAV1.tMCK.human-alpha-sarcoglycan gene transfer via intramuscular injection to the EDB muscle | Measured throughout the study | Yes | |
Secondary | Human-alpha-sarcoglycan gene expression at the site of gene transfer via muscle biopsy | First cohort: Measured 45 days for two patients and at 90 days after gene transfer for one patient; Second cohort: Measured at 6 months after gene transfer for the three patients | Yes | |
Secondary | Muscle strength of the gene transferred muscle via maximal volume isometric contraction testing (MVICT) if selected muscle is suitable for strenght testing | Measured 45 or 90 days after gene transfer in the first cohort, or 6 months post-gene transfer in second cohort depending on muscle biopsy date | No |
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