Multiple SclerosisNCT06171334
Remote Ischemic Conditioning in PPMS
A study testing Remote ischemic conditioning in people with Multiple Sclerosis, run by University of Calgary at 1 site in Canada.
Trial summary
Progressive MS remains the most difficult therapeutic challenge. Remyelination is a promising therapeutic strategy but an effective pharmacologic intervention remains elusive. Remote ischemic conditioning (RIC) is a non-pharmacologic intervention that has been studied in the context of stroke, where transient limb… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Remote ischemic conditioning
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteCanada
- Study dates
- 1 Jul 2024to 1 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained
- Men and women aged of 18 and 65 years inclusive
- With Primary Progressive Multiple Sclerosis, according to current diagnostic criteria
- Screening Expanded Disability Status Scale score between 4.0 and 6.5 inclusive
- Screening timed 25-foot walk (average of two trials) of 5.5 seconds or more
Who cannot join
- Patients whose screening MRI scan shows gadolinium enhancing lesions
- Patients with known renal insufficiency
- Patients with known significant hepatic impairment
- Patients with known allergy to gadolinium MRI contrast agent
- Patients currently using immune-modulators such as ocrelizumab or hydroxychloroquine
- Patients currently using therapeutic anticoagulation (blood thinners, such as warfarin, apixaban, rivaroxaban, dabigatran, enoxaparin)
Show all 13Show fewer
- Patients currently using Fampridine or 4-aminopyridine
- Patients planning to start Fampridine or 4-aminopyridine during the study period
- Patients planning to start Baclofen or Tizanidine during the duration of the study
- Patients who increase the dose of Baclofen or Tizanidine during the study period
- Patients who receive treatment with Botulinum toxin in the leg muscles during the study period
- Patients who are unable or unwilling to undergo gadolinium enhanced MRI scans
- Patients with known history of thrombotic events in the upper extremities
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Open-label, Single-center, Single-arm Futility Trial Evaluating Daily Remote Ischemic Conditioning for Reducing Progression of Disability in Patients With Primary Progressive Multiple Sclerosis (PPMS)
Progressive MS remains the most difficult therapeutic challenge. Remyelination is a promising therapeutic strategy but an effective pharmacologic intervention remains elusive. Remote ischemic conditioning (RIC) is a non-pharmacologic intervention that has been studied in the context of stroke, where transient limb ischemia leads to neuroprotection. However, RIC has not yet been studied in MS. The investigators hypothesized that repeating RIC over several days may induce molecular/cellular changes in the CNS that promote remyelination. Since RIC is safe, tolerable and ready for clinical translation (recent stroke trials have shown promise), the investigators will run a clinical study to test RIC in people with primary progressive MS.
The purpose of this clinical trial is to determine if RIC in a dose of 4 cycles daily can prevent worsening of walking ability in people PPMS. The trial is funded through MS Canada as well as a private donation to the Hotchkiss Brain Institute MS Translational Clinical Trials Research Program and the University of Calgary. There is no sponsorship from the pharmaceutical industry.
Read the detailed description
Remote Ischemic conditioning (RIC): Ischemic-preconditioning entails inducing short periods of cyclical tissue ischemia that confers subsequent protection against ischemia-reperfusion-injury. The rationale is that short periods of ischemia do not cause irreversible injury, but instead induce an endogenous protective environment. This short period of ischemia is not injurious, and it triggers endogenous protective signals (such as anti-inflammatory and antioxidant molecules) that reach distant organs, such as the heart, liver or the CNS. As an endogenous, non-specific response, the mechanisms involved in RIC are complex and include inflammation, oxidative stress, changes in endothelial function, cell survival etc.
Current treatments for progressive Multiple Sclerosis (the immune-modulators Siponimod and Ocrelizumab) are only modestly effective and primarily benefit people with active inflammatory disease activity (recent relapses and/or enhancing lesions on MRI). Progression free of inflammatory activity is characterized by slow accumulation of disability, greatly affecting quality of life in people with Multiple Sclerosis (MS). The investigators believe RIC is ideally suited to be tested as a therapy for progression in MS. Recent clinical trials in vascular disease have shown that daily RIC can be performed for up to a year and suggested an all-cause mortality benefit. In a recent (RICAMIS trial, 2022) multicenter, randomized trial of people with acute ischemic stroke (> 1,000 participants), 14-day RIC treatment led to improved functional outcomes at 6-months. No serious side effects were reported, and tolerability was good.
This important study was the first phase III trial to find a "protective" effect for RIC in neurological disease, and highlights the timeliness and potential for re-purposing RIC as a therapy for MS.
In this trial, the investigators will investigate whether RIC treatment can prevent disability worsening in people with Primary Progressive MS (PPMS).
The primary objective of this trial is to demonstrate non-futility of RIC for reducing progression of disability, as measured with the timed 25-foot walk (T25FW), in people with PPMS.
This is a phase II open-label, single-center, single-arm futility trial. The study will follow the Simon-2-stage MiniMax design for futility studies.
- Conditions
- Multiple Sclerosis
- Being tested
- Remote ischemic conditioning
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic conditioningDevice
The intervention consists in Remote Ischemic conditioning (RIC), one session of 40-minutes duration per day for 12 months. The procedure will be performed by using an electric auto-control device by SnapDx Inc (Calgary, Canada) with a blood pressure cuff that inflates up to a pressure of 200 mmHg during the ischemic period. Participant will self-administer the RIC procedure at their home. The device records and documents each RIC cycle.
| Study group | Role | What they receive |
|---|---|---|
| RIC | Experimental | Not described Receives: Device: Remote ischemic conditioning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Timed 25-foot walk
The primary endpoint in this study will be the worsening of disability, defined as an increase by 20% or more in the timed 25-foot walk (average of two trials) at 12 months follow-up compared to baseline.
Measured: 12 MONTHS
Secondary outcomes (3)
Nine Hole Peg Test
A validated test of upper limb motor function. Increased times (longer time to finish test). indicates worse function. A 20% change is considered significant.
Measured: 12 MONTHS
MRI measure of remyelination
MRI will be done at baseline and at 12-months. Normal appearing white matter Diffusion Tensor Imaging. Provides a numeric value, whew higher values indicate "improved" myelin integrity. The investigators will test changes in this MRI measure over time.
Measured: 12 MONTHS
SDMT (Single digit modalities test)
A validated test of processing speed (an aspect of cognition). Lower numbers indicate worse processing speed. An 8-point change is considered significant.
Measured: 12 MONTHS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2023
- Study start1 Jul 2024 (estimated)
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
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 Multiple SclerosisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase II open-label, single-center, single-arm futility trial. The study will follow the Simon-2-stage MiniMax design for futility studies.
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06171334
- Sponsor's protocol ID
- REB23-1062
- Status last verified
- Nov 2023
- First submitted
- 27 Nov 2023
- Last updated
- 9 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data may be shared to qualified researchers, upon reasonable request, after the end of study and primary data analysis.
Publications
Chen HS, Cui Y, Li XQ, Wang XH, Ma YT, Zhao Y, Han J, Deng CQ, Hong M, Bao Y, Zhao LH, Yan TG, Zou RL, Wang H, Li Z, Wan LS, Zhang L, Wang LQ, Guo LY, Li MN, Wang DQ, Zhang Q, Chang DW, Zhang HL, Sun J, Meng C, Zhang ZH, Shen LY, Ma L, Wang GC, Li RH, Zhang L, Bi C, Wang LY, Wang DL; RICAMIS Investigators. Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial. JAMA. 2022 Aug 16;328(7):627-636. doi: 10.1001/jama.2022.13123.
PubMed 35972485Camara-Lemarroy CR, Metz L, Smith EE, Dunn JF, Yong VW. Expanding the Potential Therapeutic Options for Remote Ischemic Preconditioning: Use in Multiple Sclerosis. Front Neurol. 2018 Jun 19;9:475. doi: 10.3389/fneur.2018.00475. eCollection 2018. No abstract available.
PubMed 29971043
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Single-center, Single-arm Futility Trial Evaluating Daily Remote Ischemic Conditioning for Reducing Progression of Disability in Patients With Primary Progressive Multiple Sclerosis (PPMS)
- ClinicalTrials.gov ID
- NCT06171334
- Acronym / sponsor ID
- REB23-1062
- Conditions
- Multiple Sclerosis
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 1 Jul 2024 (estimated)
- Primary completion
- 1 Mar 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 14 Dec 2023 (actual)
- 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.
Progressive MS remains the most difficult therapeutic challenge. Remyelination is a promising therapeutic strategy but an effective pharmacologic intervention remains elusive. Remote ischemic conditioning (RIC) is a non-pharmacologic intervention that has been studied in the context of stroke, where transient limb ischemia leads to neuroprotection. However, RIC has not yet been studied in MS. The investigators hypothesized that repeating RIC over several days may induce molecular/cellular changes in the CNS that promote remyelination. Since RIC is safe, tolerable and ready for clinical translation (recent stroke trials have shown promise), the investigators will run a clinical study to test RIC in people with primary progressive MS.
The purpose of this clinical trial is to determine if RIC in a dose of 4 cycles daily can prevent worsening of walking ability in people PPMS. The trial is funded through MS Canada as well as a private donation to the Hotchkiss Brain Institute MS Translational Clinical Trials Research Program and the University of Calgary. There is no sponsorship from the pharmaceutical industry.
Detailed description
Remote Ischemic conditioning (RIC): Ischemic-preconditioning entails inducing short periods of cyclical tissue ischemia that confers subsequent protection against ischemia-reperfusion-injury. The rationale is that short periods of ischemia do not cause irreversible injury, but instead induce an endogenous protective environment. This short period of ischemia is not injurious, and it triggers endogenous protective signals (such as anti-inflammatory and antioxidant molecules) that reach distant organs, such as the heart, liver or the CNS. As an endogenous, non-specific response, the mechanisms involved in RIC are complex and include inflammation, oxidative stress, changes in endothelial function, cell survival etc.
Current treatments for progressive Multiple Sclerosis (the immune-modulators Siponimod and Ocrelizumab) are only modestly effective and primarily benefit people with active inflammatory disease activity (recent relapses and/or enhancing lesions on MRI). Progression free of inflammatory activity is characterized by slow accumulation of disability, greatly affecting quality of life in people with Multiple Sclerosis (MS). The investigators believe RIC is ideally suited to be tested as a therapy for progression in MS. Recent clinical trials in vascular disease have shown that daily RIC can be performed for up to a year and suggested an all-cause mortality benefit. In a recent (RICAMIS trial, 2022) multicenter, randomized trial of people with acute ischemic stroke (> 1,000 participants), 14-day RIC treatment led to improved functional outcomes at 6-months. No serious side effects were reported, and tolerability was good.
This important study was the first phase III trial to find a "protective" effect for RIC in neurological disease, and highlights the timeliness and potential for re-purposing RIC as a therapy for MS.
In this trial, the investigators will investigate whether RIC treatment can prevent disability worsening in people with Primary Progressive MS (PPMS).
The primary objective of this trial is to demonstrate non-futility of RIC for reducing progression of disability, as measured with the timed 25-foot walk (T25FW), in people with PPMS.
This is a phase II open-label, single-center, single-arm futility trial. The study will follow the Simon-2-stage MiniMax design for futility studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase II open-label, single-center, single-arm futility trial. The study will follow the Simon-2-stage MiniMax design for futility studies.
| Arm | Type | Receives |
|---|---|---|
| RIC | Experimental | Device: Remote ischemic conditioning |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent obtained
- Men and women aged of 18 and 65 years inclusive
- With Primary Progressive Multiple Sclerosis, according to current diagnostic criteria
- Screening Expanded Disability Status Scale score between 4.0 and 6.5 inclusive
- Screening timed 25-foot walk (average of two trials) of 5.5 seconds or more
Key exclusion criteria (13 listed)
- Patients whose screening MRI scan shows gadolinium enhancing lesions
- Patients with known renal insufficiency
- Patients with known significant hepatic impairment
- Patients with known allergy to gadolinium MRI contrast agent
- Patients currently using immune-modulators such as ocrelizumab or hydroxychloroquine
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 |
|---|---|---|
| Remote ischemic conditioningThe intervention consists in Remote Ischemic conditioning (RIC), one session of 40-minutes duration per day for 12 months. The procedure will be performed by using an electric auto-control device by SnapDx Inc (Calgary, Canada) with a blood pressure cuff that inflates up to a pressure of 200 mmHg during the ischemic period. Participant will self-administer the RIC procedure at their home. The device records and documents each RIC cycle. | Device | RIC |
Primary outcome
Timed 25-foot walk
Time frame: 12 MONTHS
The primary endpoint in this study will be the worsening of disability, defined as an increase by 20% or more in the timed 25-foot walk (average of two trials) at 12 months follow-up compared to baseline.
3 secondary outcomes
Nine Hole Peg Test
Time frame: 12 MONTHS
MRI measure of remyelination
Time frame: 12 MONTHS
SDMT (Single digit modalities test)
Time frame: 12 MONTHS
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2024.
- Background: PubMed 35972485Chen HS, Cui Y, Li XQ, Wang XH, Ma YT, Zhao Y, Han J, Deng CQ, Hong M, Bao Y, Zhao LH, Yan TG, Zou RL, Wang H, Li Z, Wan LS, Zhang L, Wang LQ, Guo LY, Li MN, Wang DQ, Zhang Q, Chang DW, Zhang HL, Sun J, Meng C, Zhang ZH, Shen LY, Ma L, Wang GC, Li RH, Zhang L, Bi C, Wang LY, Wang DL; RICAMIS Investigators. Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial. JAMA. 2022 Aug 16;328(7):627-636. doi: 10.1001/jama.2022.13123.
- Background: PubMed 29971043Camara-Lemarroy CR, Metz L, Smith EE, Dunn JF, Yong VW. Expanding the Potential Therapeutic Options for Remote Ischemic Preconditioning: Use in Multiple Sclerosis. Front Neurol. 2018 Jun 19;9:475. doi: 10.3389/fneur.2018.00475. eCollection 2018. No abstract available.
- Individual participant dataSharing planned: Yes. De-identified data may be shared to qualified researchers, upon reasonable request, after the end of study and primary data analysis.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remote ischemic conditioning in people with Multiple Sclerosis, run by University of Calgary at 1 site in Canada.
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 5 inclusion and 13 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: opening soon, as of the sponsor's last update on 9 May 2024. 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Timed 25-foot walk (time frame: 12 MONTHS). 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 NCT06171334, 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 9 May 2024.