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

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ClinicalTrials.gov Identifier: NCT02941328
Recruitment Status : Completed
First Posted : October 21, 2016
Last Update Posted : February 5, 2018
Sponsor:
Information provided by (Responsible Party):
Camiel Wijngaarde, UMC Utrecht

Tracking Information
First Submitted Date  ICMJE September 30, 2016
First Posted Date  ICMJE October 21, 2016
Last Update Posted Date February 5, 2018
Actual Study Start Date  ICMJE December 2015
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2016)
  • MFM (Motor Function Measurement). [ Time Frame: change over the course of 8 weeks compared to baseline ]
    D1+D2+D3 but also D1, D2, or D3 sub scores of the MFM scales will be used.
  • repeated nine-hole peg test performance [ Time Frame: Change in performance (in time to complete) the test rounds over the course of 8 weeks of medication compared to baseline ]
    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)).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2016)
  • endurance nine hole peg test [ Time Frame: Change in performance after 8 weeks of therapy (placebo or mestinon). ]
    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
  • endurance box-and-block test [ Time Frame: Change in performance after 8 weeks of therapy (placebo or mestinon) ]
    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.
  • endurance walk test [ Time Frame: Change in performance after 8 weeks of therapy (placebo or mestinon). ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SPACE Trial: Pyridostigmine vs Placebo in SMA Types 2, 3 and 4
Official Title  ICMJE A Phase II, Mono-center, Placebo-controlled, Double-blind, Crossover Trial to Investigate Effect and Efficacy of Pyridostigmine in Dutch Patients With Spinal Muscular Atrophy Types 2, 3 and 4
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.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Spinal Muscular Atrophy
  • SMA
  • Kugelberg-Welander Disease
Intervention  ICMJE
  • Drug: Pyridostigmine
    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)
    Other Name: Mestinon
  • Drug: Placebo
    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)
Study Arms  ICMJE
  • Experimental: Pyridostigmine
    (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).
    Intervention: Drug: Pyridostigmine
  • Placebo Comparator: Placebo
    (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).
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 1, 2018)
39
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2016)
50
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02941328
Other Study ID Numbers  ICMJE NL38048.041.14
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Camiel Wijngaarde, UMC Utrecht
Study Sponsor  ICMJE UMC Utrecht
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: W.L. Van der Pol, MD, PhD UMC Utrecht
PRS Account UMC Utrecht
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP