A trial investigating the effects of pyridostigmine (mestinon) versus a placebo in a double-blind cross over trial in patients with hereditary proximal spinal muscular atrophy (SMA) types 2, 3 and 4.
In this cross-over trial we will investigate the effects of pyridostigmine (mestinon) versus a placebo on fatigability in patients with hereditary proximal spinal muscular atrophy (SMA) types 2, 3 and 4 (aged 12 and older) The study participants will be using a placebo during 8 weeks and mestinon during 8 weeks. Both investigators and patients are blinded to the treatment allocation in both periods. Patients will be randomly assigned to use placebo or mestinon first. At the end of the study, patients will have used both mestinon and a placebo during 8 weeks. In both phases (periods) of the cross over study, study medication dosage will slowly be increased to a maximum dosage of 6 mg/kg/day (spread over 4 doses daily) in order to either prevent side effects or to manage them as good as possible. This scheme allows us to assist our participants in case side effects do occur early. Although we strive to have all patients on the same dosage per kg of body weight, serious side effects will obviously lead to lowering the dosage. Before the start of medication use (either placebo or pyridostigmine), baseline measurements will be taken: a physical examination and data concerning both primary and secondary outcomes (MFM, MRC scores, fatigability tests, etc.) will be collected. After use a drug (mestinon/placebo) for 8 weeks these tests will be repeated, to evaluate possible medication effect. After a wash-out period of approximately 1-2 weeks the same scheme is used for the second study period (i.e. the cross-over design). Unblinding follows after the entire study is completed (i.e.: last included patients finishes participation).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
39
Pyridostigmine, administered orally starting with 2mg/kg/day (in 4 daily doses, i.e. 0,5mg/kg/dose) and slowly increasing to a maximum dosage of 6mg/kg/day (4 daily doses of 1,5mg/kg/day)
Placebo administered orally starting with 2mg/kg/day (in 4 daily doses, i.e. 0,5mg/kg/dose) and slowly increasing to a maximum dosage of 6mg/kg/day (4 daily doses of 1,5mg/kg/day)
University Medical Center of Utrecht (UMCU)
Utrecht, Netherlands
MFM (Motor Function Measurement).
D1+D2+D3 but also D1, D2, or D3 sub scores of the MFM scales will be used.
Time frame: change over the course of 8 weeks compared to baseline
repeated nine-hole peg test performance
The time needed tot complete multiple rounds of the nine hole peg test (hence: repeated NHPT) will be recorded (visit 1) and compared to the performance on the test after 8 weeks of treatment (placebo or mestinon) (visit 2). Visit 3 will serve as the baseline measurement for the 2nd study period (again followed by 8 weeks of treatment and the final study visit (visit 4)).
Time frame: Change in performance (in time to complete) the test rounds over the course of 8 weeks of medication compared to baseline
endurance nine hole peg test
During the endurance tests, patients will perform at 75% of their maximum performance. Differences in before and after treatment results (number of rounds completed) will be analysed
Time frame: Change in performance after 8 weeks of therapy (placebo or mestinon).
endurance box-and-block test
During the endurance tests, patients will perform at 75% of their maximum performance. Differences in before and after treatment results (number of rounds completed) will be analysed. This test will be performed only if the patient is capable of performing it.
Time frame: Change in performance after 8 weeks of therapy (placebo or mestinon)
endurance walk test
During the endurance tests, patients will perform at 75% of their maximum performance. Differences in before and after treatment results (e.d. total distance travelled) will be analysed. This test will be performed only if the patient is able to walk.
Time frame: Change in performance after 8 weeks of therapy (placebo or mestinon).
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