Randomized, double‐blind trial of mazindol in Duchenne dystrophy

Abstract

There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.

Evolving Therapeutic Strategies for Duchenne Muscular Dystrophy: Targeting Downstream Events

“…Conversely, daily administration of mazindol to five DMD patients for 3 mo yielded no improvement in function but did produce adverse effects such as irritability, sleep disturbances, and elevated heart rate (23). In addition, a subsequent investigation showed that mazindol treatment of 83 boys with DMD for a 12-mo trial did not slow the progression of muscle weakness, but did slow gain in height of the boys (24). More recently, the possibility that exogenous GH could reduce DMD pathology has been revisited, with a particular focus on a potential ameliorative effect on DMD cardiomyopathy (25).…”

Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers

“…As with [47,48], our data suggest that lower IGF-1 circulating levels are more related to a severe than to a benign clinical form of muscular dystrophy.…”

“…As a result, the same authors pointed out that GH inhibitors, such as mazindol, should be used to treat Duchenne muscular dystrophy [45,46]. In contrast, it has been reported that mazindol does not slow the progression of Duchenne dystrophy [47,48] and cause several adverse effects in boys after long term use [48]. The latter studies used IGF-1 determination, which is more accurate than L-DOPA, more stable during the day and does not suffer large secretion oscillations as seen with GH [42,43,26].…”

Regeneration-blocked mdx muscle: in vivo model for testing treatments

“…DMD patients are debilitated, having compromised respiratory and cardiac function, and are therefore at increased risk for side effects of the test treatment. 4,5,16 Even with multicenter design, testing therapies in boys with DMD is slow (once enrolled, patients must be followed for 6-18 months). 4,5,16 The RB-mdx treatment test approach carries no patient risk and still yields clinically relevant in vivo data, costs much less, and tests therapies more quickly.…”