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

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2011-004369-34-NL
• Date of registration: 03/11/2014
• Prospective Registration: Yes
• Primary sponsor: Universtiy Medical Center Utrecht
• Public title: 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
• Scientific title: SPACE trial SMA and Pyridostigmine in Adults and Children; Efficacy trial Phase II, mono-center, doubleblind, placebo-controlled, crossover trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2, 3 and 4 - SPACE trial
• Date of first enrolment: 22/04/2015
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004369-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: METC
• Affiliation: UMC Utrecht

• Name: METC
• Affiliation: UMC Utrecht

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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.
MedDRA version: 17.1 Level: LLT Classification code 10068209 Term: Spinal muscular atrophy adult onset System Organ Class: 100000004850
MedDRA version: 17.1 Level: LLT Classification code 10051203 Term: Spinal muscular atrophy congenital System Organ Class: 100000004850

Intervention(s)

Trade Name: pyridostigmine bromide
Product Name: Mestinon
Product Code: RVG 03820
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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 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

Secondary Outcome(s)

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.

Secondary ID(s)

UMC-NMZ-SMA2011

Source(s) of Monetary Support

Prinses Beatrix Fonds

Ethics review

Status: Approved
Approval date:
Contact: