Post by David Feder on Mar 25, 2008 19:36:38 GMT -5
Probably pentoxyfilline can't help in DMD.
Immediate Release Oral Pentoxifylline Is Poorly Tolerated in Duchenne Muscular Dystrophy Boys
OBJECTIVE: The objective of this open label pilot study of oral, immediate release pentoxifylline was to assess the tolerability, safety and efficacy on muscle strength and function in Duchenne Muscular Dystrophy (DMD). BACKGROUND: Severe to complete dystrophin deficiency produces the DMD phenotype. Untreated DMD boys demonstrate progressive, eventually fatal, muscle weakness. In relevant animal models, pentoxifylline slows disease progression. DESIGN/METHODS: This was an open label, prospective study with a 3 month lead in period followed by 12 months of treatment with a 20mg/kg/day dose of pentoxifylline (maximal dose 598 mg/day). Study subjects were 4-9 year old steroid-naive DMD boys. The primary efficacy measure was a total quantitative muscle testing (QMT) score. Secondary and exploratory endpoint measures were manual muscle strength (MMT), arm and leg QMT, timed function tests, muscle MRI, serum TNF- and TGF- levels and adverse event profiles. RESULTS: Of twenty patients screened, 17 enrolled and 9 completed the protocol. Age range was 4.3-8.5 years (mean 6.0, median 5.8). QMT and MMT measures did not show a significant change during the 3 month lead-in or 12 month treatment period. Five of 8 patient withdrawals were due to intolerable adverse events. Eleven of 17 patients experienced nausea and vomiting. Two patients experienced moderate (grade 3) to severe (grade 4) leucopenia. CONCLUSIONS/RELEVANCE: The immediate release oral formulation of pentoxifylline is not well tolerated in children with DMD. The 12% incidence of leucopenia in this study was higher than the reported incidence rate in adults (<1%). Leucopenia improved post drug withdrawal. The 65% incidence of vomiting was also higher than reported in adults (4.5%). The lack of deterioration in strength and function over 12 months in steroid naive DMD children (mean age 6 years) suggests a possible beneficial effect on disease progression and warrants further study with a different formulation of pentoxifylline.
Pentoxifylline Treatment Fails To Rescue Muscle Strength and Function Deterioration in Prednisone-Treated Duchenne Muscular Dystrophy
OBJECTIVE: This clinical trial was conducted to evaluate the additive effect of Pentoxyfylline to prednisone by stabilizing or improving muscle strength and function in DMD. BACKGROUND: Treatment of DMD with prednisone results in slowing, but not prevention, of deterioration of muscle strength and function. Pentoxyfylline is an anti-inflammatory and anti-fibrotic drug that prevents muscle strength deterioration by 51% in the exercised mdx mouse model of the disease. If these effects translate to human, a combination therapy could halt disease progression, or produce a steroid sparing effect. DESIGN/METHODS: This was a randomized, controlled, double-blind 12 months study of Pentoxyfylline in steroid-treated DMD boys over the age of 7. The primary objective of the study was to determine whether daily treatment with PTX could significantly improve total QMT score at 12 months compared to patients receiving placebo. Secondary endpoints were QMT arm and leg scores, grip, MMT score, timed function, quality of life and exploratory surrogate outcome measurements of levels of TGF- and TNF-. Safety laboratory assessments and adverse events were collected. RESULTS: Based on preliminary results, seventy three patients were enrolled, 64 randomized and 57 completed the protocol. Mean and median age were 10.07 and 9.5 respectively. Baseline characteristics between groups were not statistically significant. Total QMT score changes at 12 months was not significantly different between groups (p=0.5). None of the secondary strength and functional endpoints differed between groups at 12 months. The PTX group presented with increase incidence of coagulation, skin and mild gastrointestinal side effects. CONCLUSIONS/RELEVANCE: This study has shown that Pentoxyfylline treatment, although well tolerated over a year, has no effect in slowing disease progression over prednisone in DMD boys.
Immediate Release Oral Pentoxifylline Is Poorly Tolerated in Duchenne Muscular Dystrophy Boys
OBJECTIVE: The objective of this open label pilot study of oral, immediate release pentoxifylline was to assess the tolerability, safety and efficacy on muscle strength and function in Duchenne Muscular Dystrophy (DMD). BACKGROUND: Severe to complete dystrophin deficiency produces the DMD phenotype. Untreated DMD boys demonstrate progressive, eventually fatal, muscle weakness. In relevant animal models, pentoxifylline slows disease progression. DESIGN/METHODS: This was an open label, prospective study with a 3 month lead in period followed by 12 months of treatment with a 20mg/kg/day dose of pentoxifylline (maximal dose 598 mg/day). Study subjects were 4-9 year old steroid-naive DMD boys. The primary efficacy measure was a total quantitative muscle testing (QMT) score. Secondary and exploratory endpoint measures were manual muscle strength (MMT), arm and leg QMT, timed function tests, muscle MRI, serum TNF- and TGF- levels and adverse event profiles. RESULTS: Of twenty patients screened, 17 enrolled and 9 completed the protocol. Age range was 4.3-8.5 years (mean 6.0, median 5.8). QMT and MMT measures did not show a significant change during the 3 month lead-in or 12 month treatment period. Five of 8 patient withdrawals were due to intolerable adverse events. Eleven of 17 patients experienced nausea and vomiting. Two patients experienced moderate (grade 3) to severe (grade 4) leucopenia. CONCLUSIONS/RELEVANCE: The immediate release oral formulation of pentoxifylline is not well tolerated in children with DMD. The 12% incidence of leucopenia in this study was higher than the reported incidence rate in adults (<1%). Leucopenia improved post drug withdrawal. The 65% incidence of vomiting was also higher than reported in adults (4.5%). The lack of deterioration in strength and function over 12 months in steroid naive DMD children (mean age 6 years) suggests a possible beneficial effect on disease progression and warrants further study with a different formulation of pentoxifylline.
Pentoxifylline Treatment Fails To Rescue Muscle Strength and Function Deterioration in Prednisone-Treated Duchenne Muscular Dystrophy
OBJECTIVE: This clinical trial was conducted to evaluate the additive effect of Pentoxyfylline to prednisone by stabilizing or improving muscle strength and function in DMD. BACKGROUND: Treatment of DMD with prednisone results in slowing, but not prevention, of deterioration of muscle strength and function. Pentoxyfylline is an anti-inflammatory and anti-fibrotic drug that prevents muscle strength deterioration by 51% in the exercised mdx mouse model of the disease. If these effects translate to human, a combination therapy could halt disease progression, or produce a steroid sparing effect. DESIGN/METHODS: This was a randomized, controlled, double-blind 12 months study of Pentoxyfylline in steroid-treated DMD boys over the age of 7. The primary objective of the study was to determine whether daily treatment with PTX could significantly improve total QMT score at 12 months compared to patients receiving placebo. Secondary endpoints were QMT arm and leg scores, grip, MMT score, timed function, quality of life and exploratory surrogate outcome measurements of levels of TGF- and TNF-. Safety laboratory assessments and adverse events were collected. RESULTS: Based on preliminary results, seventy three patients were enrolled, 64 randomized and 57 completed the protocol. Mean and median age were 10.07 and 9.5 respectively. Baseline characteristics between groups were not statistically significant. Total QMT score changes at 12 months was not significantly different between groups (p=0.5). None of the secondary strength and functional endpoints differed between groups at 12 months. The PTX group presented with increase incidence of coagulation, skin and mild gastrointestinal side effects. CONCLUSIONS/RELEVANCE: This study has shown that Pentoxyfylline treatment, although well tolerated over a year, has no effect in slowing disease progression over prednisone in DMD boys.
