SPACE Trial: Pyridostigmine vs Placebo in SMA Types 2, 3 and 4

NCT02941328 | Completed Phase 2

• 1 other identifier: NL38048.041.14
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Spinal Muscular Atrophy; SMA; Kugelberg-Welander Disease

Keywords

SMA, SMN1, Kugelberg-Welander

Outcome Measures

Primary Outcomes (2)

• MFM (Motor Function Measurement).

  D1+D2+D3 but also D1, D2, or D3 sub scores of the MFM scales will be used.

  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)).

  Change in performance (in time to complete) the test rounds over the course of 8 weeks of medication compared to baseline

Secondary Outcomes (3)

• endurance nine hole peg test

  Change in performance after 8 weeks of therapy (placebo or mestinon).

• endurance box-and-block test

  Change in performance after 8 weeks of therapy (placebo or mestinon)

• endurance walk test

  Change in performance after 8 weeks of therapy (placebo or mestinon).

Study Arms (2)

Pyridostigmine

EXPERIMENTAL

(this is a cross-over trial, in which participants will receive both a placebo and pyridostigmine in different study periods. Both investigators and participants are blinded for what medication is used in what period. All patients will eventually use a placebo for 8 weeks and pyridostigmine for 8 weeks).

Drug: Pyridostigmine

Placebo

PLACEBO COMPARATOR

(this is a cross-over trial, in which participants will receive both a placebo and pyridostigmine in different study periods. Both investigators and participants are blinded for what medication is used in what period. All patients will eventually use a placebo for 8 weeks and pyridostigmine for 8 weeks).

Drug: Placebo

Interventions

Pyridostigmine DRUG

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)

Also known as: Mestinon

Pyridostigmine

Placebo DRUG

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)

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A clinical diagnosis of SMA type 2, 3a, 3b or 4
• Genetically confirmed homozygous SMN1 deletion
• Ability to complete visits during trial period;
• Given oral and written informed consent when ≥18 years old;
• Given informed consent by the parents or legal representative(s) in case of patients aged ≥12 till \<18 years old (in accordance with Dutch law)
• Ability of performing at least 2 subsequent rounds of the Nine Hole Peg test
• A maximum total Motor Function Measure (MFM) score of 80% (i.e.: a maximum score under 80% of the D1+D2+D3 subscores).

You may not qualify if:

• Known concomitant disorders of the NMJ (e.g. but not limited to: Lambert Eaton myasthenic syndrome, myasthenia gravis);
• Use of drugs that may alter NMJ function
• Classic SMA type 1;
• Apprehension against participation in EMG;
• Inability to meet study visits;
• Mechanical gastro-intestinal, urinary or biliary obstruction;
• 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;
• ECG abnormalities known as a contraindication for pyridostigmine use;
• Current pregnancy or breast-feeding
• Allergy to bromides
• Severe bronchial asthma (in case of uncertainty of diagnosis, we will contact treating pulmonologist or physician)
• Total MFM score at baseline (screening) \> 80% (i.e.: a maximum total MFM score above 80% of the D1+D2+D3 subscores).

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

University Medical Center of Utrecht (UMCU)

Utrecht, 3584 CX, Netherlands

Location

Related Publications (2)

• Stam M, Wijngaarde CA, Bartels B, Asselman FL, Otto LAM, Habets LE, van Eijk RPA, Middelkoop BM, Goedee HS, de Groot JF, Roes KCB, Schoenmakers MAGC, Nieuwenhuis EES, Cuppen I, van den Berg LH, Wadman RI, van der Pol WL. Randomized double-blind placebo-controlled crossover trial with pyridostigmine in spinal muscular atrophy types 2-4. Brain Commun. 2022 Dec 9;5(1):fcac324. doi: 10.1093/braincomms/fcac324. eCollection 2023.

  PMID: 36632180 DERIVED

• Stam M, Wadman RI, Wijngaarde CA, Bartels B, Asselman FL, Otto LAM, Goedee HS, Habets LE, de Groot JF, Schoenmakers MAGC, Cuppen I, van den Berg LH, van der Pol WL. Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2-4 (SPACE trial). BMJ Open. 2018 Jul 30;8(7):e019932. doi: 10.1136/bmjopen-2017-019932.

  PMID: 30061431 DERIVED

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Spinal Muscular Atrophy, Type IV

Interventions

Pyridostigmine Bromide

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• W.L. Van der Pol, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 30, 2016
• First Posted: October 21, 2016
• Study Start: December 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: February 5, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)