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

This study is enrolling participants by invitation only.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02941328
First Posted: October 21, 2016
Last Update Posted: October 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Camiel Wijngaarde, UMC Utrecht
  Purpose
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.

Condition Intervention Phase
Spinal Muscular Atrophy SMA Kugelberg-Welander Disease Drug: Pyridostigmine Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Camiel Wijngaarde, UMC Utrecht:

Primary Outcome Measures:
  • 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)).


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 50
Study Start Date: December 2015
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
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
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).
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)

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).

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02941328


Locations
Netherlands
University Medical Center of Utrecht (UMCU)
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
UMC Utrecht
Investigators
Principal Investigator: W.L. Van der Pol, MD, PhD UMC Utrecht
  More Information

Responsible Party: Camiel Wijngaarde, MD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT02941328     History of Changes
Other Study ID Numbers: NL38048.041.14
First Submitted: September 30, 2016
First Posted: October 21, 2016
Last Update Posted: October 30, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Camiel Wijngaarde, UMC Utrecht:
SMA, SMN1, Kugelberg-Welander

Additional relevant MeSH terms:
Spinal Muscular Atrophies of Childhood
Atrophy
Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Pyridostigmine Bromide
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs