This trial is evaluating whether Risdiplam will improve 3 primary outcomes and 32 secondary outcomes in patients with Muscular Atrophy. Measurement will happen over the course of Day 1 on risdiplam up to end of study (up to approximately 7 years).
This trial requires 231 total participants across 6 different treatment groups
This trial involves 6 different treatments. Risdiplam is the primary treatment being studied. Participants will be divided into 3 treatment groups. Some patients will receive a placebo treatment. The treatments being tested are in Phase 2 & 3 and have had some early promising results.
No evidence was found of cure of muscular atrophy after a period of intensive physiotherapy. Thus, a cure of muscular atrophy seems doubtful. However, a cure of muscular atrophy could not be excluded for the group of patients with muscular atrophy at the beginning of the rehabilitation program.
Muscle wasting can be induced by a few conditions. All the conditions that cause muscle wasting will also cause atrophy in muscles that attach to the muscle and that the muscle is required to innervate. Muscle wasting can be induced by malnutrition in either the young or older animals. Nutrient deficient muscles require a constant supply of fuel and ATP and a high nutrient environment for the muscles to receive their required energy. Muscle wasting can be caused by denervation (which can occur by neurological conditions causing the degeneration of nerves that would normally innervate muscle fibers) as well as muscle fibers that no longer can receive sufficient energy. Muscle atrophy can be caused by neuromuscular diseases that compromise the muscle.
Signs of muscular atrophy can include loss of the definition of the patella groove, patella-femoral offset, medial displacement of the femur, and medial displacement of the patella. The exact location and extent of these signs are individual to the patient.
Although more patients are diagnosed with muscular atrophy today, it seems that the incidence of muscular atrophy is declining. The reasons for this observation are unclear, but may relate to a decreasing incidence of anorexia nervosa and other disorders that often lead to nutritional deficiency. Therefore, the true prevalence of muscular atrophy is not known.
Muscular atrophy is the common symptom in the patient with chronic fatigue syndrome; the presence of muscular atrophy suggests the onset of the syndrome. A thorough examination in the patient with muscular atrophy is required.
Treatments can be divided into 3 categories: exercise, dietary, and injections. The exercise treatment of muscular atrophy often includes the patient performing strength training exercises that produce gains in muscular strength. This exercise may be performed on a regular or on a special weight training machine. The dietary treatments of muscular atrophy may include changing or increasing the proportion of protein in the diet in order to provide additional energy. For people who have problems swallowing, an aspiration pneumonitis may occur if they drink too much and these people should consume at least 1,000 cc per day of water. Weakness may develop if they have too small of a number of injections that will weaken the muscles.
Compared to placebo, risdiplam does not significantly affect muscle strength. People who take risdiplam do not show a change in body composition or other adverse side-effects.
[A 2006 study(https://www.neim.org/article/new-findings-in-muscular-atrophy)] reported on a major finding. When comparing the two drug regimens, the results showed a statistically and clinically significant difference between the two drug regimens. Although this analysis is only an observational study, it shows a trend of the drug regimens having an added effect in muscular atrophy. The authors think it very important that we continue to evaluate clinical trials that use the appropriate statistical analysis to show a significant difference. The authors suggested that further study in humans might also be undertaken.
The clustering of PA, GAA and muscular atrophy seems to run in families. However, the familial aggregation of GAA is limited by moderate phenotypic heterogeneity, and of PA is further limited by a small number of affected relatives. Findings from a recent study suggest that modifier genes may play a role in the pathogenesis of PA.
The most recent developments in risdiplam for therapeutic uses, with the exception of patients who experienced life-threatening thrombocytopenic purpura with or without life-threatening bleeding, are summarised in table. Risdiplam has shown to be safe and effective in treating a variety of gastrointestinal diseases and chronic muscular diseases. The dosage used in the treatment of muscular ailments has been tailored for each patient's individual needs without causing unwanted side-effects. The dose range of risdiplam that can be safely used is 10 μg/kg administered i.v. once a day or 3 μg/kg administered intramuscularly each day for 7 days.
Treatment with risdiplam was shown to be ineffective to stop atrophy of the calf muscles in patients after myopathy of the calf muscle for > or = 12 months regardless of the daily regimen used.
Clinically meaningful improvements in muscular function should be achievable in this patient population, yet it is unclear which patients are most suitable for inclusion in clinical trials. Given the many options, such as patient choice and individual trial selection, clinicians and researchers should continue their efforts to identify the most effective interventions.