Spinal Muscular AtrophyPhase 2SPACENCT02941328
SPACE Trial: Pyridostigmine vs Placebo in SMA Types 2, 3 and 4
A Phase 2 study testing Pyridostigmine in people with Spinal Muscular Atrophy and SMA, run by UMC Utrecht at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Spinal Muscular Atrophy, SMA, Kugelberg-Welander Disease
- What is being tested?
- Pyridostigmine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2015to Jan 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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;
Show all 12Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center of Utrecht (UMCU)
Utrecht, 3584 CX
About this study
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
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.
Read the 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).
- Conditions
- Spinal Muscular Atrophy, SMA, Kugelberg-Welander Disease
- Being tested
- Pyridostigmine, Placebo
- Keywords
- SMA, SMN1, Kugelberg-Welander
- Medical subject headings
- Muscular Atrophy, Spinal, Spinal Muscular Atrophies of Childhood, Spinal Muscular Atrophy, Type IV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridostigmineDrug
Also called Mestinon
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)
PlaceboDrug
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 group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MFM (Motor Function Measurement).
D1+D2+D3 but also D1, D2, or D3 sub scores of the MFM scales will be used.
Measured: 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)).
Measured: 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
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
Measured: Change in performance after 8 weeks of therapy (placebo or mestinon).
endurance box-and-block test
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.
Measured: Change in performance after 8 weeks of therapy (placebo or mestinon)
endurance walk test
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.
Measured: Change in performance after 8 weeks of therapy (placebo or mestinon).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2016 (estimated)
- Study startDec 2015
- Primary completionJan 2018
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Camiel Wijngaarde, UMC Utrecht
- Investigators
- W.L. Van der Pol, MD, PhD, Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02941328
- Sponsor's protocol ID
- NL38048.041.14
- Acronym
- SPACE
- Status last verified
- Feb 2018
- First submitted
- 30 Sep 2016
- Last updated
- 5 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 36632180Stam 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.
PubMed 30061431
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02941328
- Acronym / sponsor ID
- SPACE / NL38048.041.14
- Conditions
- Spinal Muscular Atrophy, SMA, Kugelberg-Welander Disease
- Keywords
- SMA, SMN1, Kugelberg-Welander
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 21 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyridostigmine | Experimental | Drug: 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). |
| Placebo | Placebo comparator | Drug: 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). |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PyridostigmineAlso: MestinonPyridostigmine, 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) | Drug | Pyridostigmine |
| PlaceboPlacebo 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) | Drug | Placebo |
Primary outcome
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)).
3 secondary outcomes
endurance nine hole peg test
Time frame: Change in performance after 8 weeks of therapy (placebo or mestinon).
endurance box-and-block test
Time frame: Change in performance after 8 weeks of therapy (placebo or mestinon)
endurance walk test
Time frame: Change in performance after 8 weeks of therapy (placebo or mestinon).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
- Derived from this study: PubMed 36632180Stam 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.
- Derived from this study: PubMed 30061431Stam 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
W.L. Van der Pol, MD, PhD principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyridostigmine in people with Spinal Muscular Atrophy and SMA, run by UMC Utrecht at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MFM (Motor Function Measurement). (time frame: change over the course of 8 weeks compared to baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02941328, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018.