Remote Ischemic Conditioning in PPMS

NCT06171334 | Not Yet Recruiting

• 1 other identifier: REB23-1062
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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.

  12 MONTHS

Secondary Outcomes (3)

• Nine Hole Peg Test

  12 MONTHS

• MRI measure of remyelination

  12 MONTHS

• SDMT (Single digit modalities test)

  12 MONTHS

Study Arms (1)

RIC

EXPERIMENTAL

Device: Remote ischemic conditioning

Interventions

Remote ischemic conditioning DEVICE

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.

RIC

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Canada

Location

Related Publications (2)

• 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.

  PMID: 35972485 BACKGROUND

• Camara-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.

  PMID: 29971043 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: November 27, 2023
• First Posted: December 14, 2023
• Study Start: July 1, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 9, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: After end of study and data analysis

Locations

CA (1)