SPACE trial SMA and Pyridostigmine in Adults and Children; Experimental trial to assess effect of pyridostigmine compared to placebo in patients with spinal muscular atrophy types 2, 3 and 4

Phase 1

• Conditions: MedDRA version: 17.1 Level: LLT Classification code 10068209 Term: Spinal muscular atrophy adult onset System Organ Class: 100000004850; Proximal spinal muscular atrophy (SMA) is characterized by weakness of predominantly axial and proximal muscle groups and is caused by homozygous deletion of the survival motor neuron 1 (SMN1)-gene. There are 4 SMA types (type 1-4), with a descending order of severity. Age at onset and achieved motor milestones are the characteristics to define severity. Treatment of SMA is exclusively supportive.; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]; MedDRA version: 17.1 Level: LLT Classification code 10051203 Term: Spinal muscular atrophy congenital System Organ Class: 100000004850

• Registration Number: EUCTR2011-004369-34-NL
• Lead Sponsor: niverstiy Medical Center Utrecht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-11-03
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 45

Inclusion Criteria

Patients with SMA will be included following the predefined criteria: 1) a clinical diagnosis of SMA type 2, 3a, 3b or 4 and a genetically confirmed homozygous SMN1 deletion 2) ability to complete visits during trial period; 3) given oral and written informed consent when =18 years old; 4) given informed consent by the parents or legal representative in case of patients aged <18 years old; 5) ability of performing the Nine Hole Peg test within 50 seconds
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

Exclusion criteria for patients are 1) known concomitant disorders of the NMJ (Lambert Eaton myasthenic syndrome, myasthenia gravis); 2) use of drugs that may alter NMJ function; 3) SMA type 1; 4) apprehension against participation in EMG; 5) inability to meet study visits; 6) mechanical gastro-intestinal, urinary or biliary obstruction; 6) clinical significant alterations of laboratory tests (electrolytes, liver function, kidney function, thyroid function or blood dysplasia) drawn within 14 days prior to start of study entry; 7) electrocardiofysiology abnormalities known as a contraindication for pyridostigmine use; 8) pregnancy 9) allergy to bromides 10) bronchial astma

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of this placebo-controlled cross-over trial in adult patients with SMA type 2, 3 and 4 is to investigate the effect and efficacy of pyridostigmine on muscle strength and fatiquabillity in patients with SMA. ;Secondary Objective: Secondary outcome measures are the effect of pyridostigmine on neurofysiologic parameters and subjective scales;Primary end point(s): Change in Nine Hole Peg test and Motor Function Measure;Timepoint(s) of evaluation of this end point: Patients will be screened. Clinical evaluation in patients will take place 2 times in de treatmentperiod of 8 weeks; at te start and at the end.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary outcome measures are scores on Vigori Measurement, scales on daily activities and presence of decrement upon repetitive nerve stimulation, quality of and activity in life scores, and adverse events.;Timepoint(s) of evaluation of this end point: Clinical evaluation in patients will take place 2 times in de treatmentperiod of 8 weeks; at te start and at the end.