EXpain Trial - Exercise an a Non-pharmacological Pain-relieving Treatment in People With Multiple Sclerosis

NCT07342777 | Recruiting DMC

• 1 other identifier: EXpain Trial
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

The primary goal of this study is to test whether 12 weeks of progressive resistance exercise is an effective non-pharmacological treatment for reducing pain in people with multiple sclerosis and chronic pain. The study will be a randomized controlled trial with multiple training sites. After baseline testing, participants will be randomly assigned to either a 12-week progressive resistance exercise intervention followed by a 12-week follow-up period or to a 24-week waitlist control group that receives usual care. It is hypothesized that people with multiple sclerosis and chronic pain who receive the intervention will experience greater reductions in pain (i.e., clinically relevant reductions) compared to the waitlist control group (primary hypothesis), and that this pain reduction will be preserved after a 12-week follow-up period (secondary hypothesis).

Conditions

Multiple Sclerosis; Chronic Pain; Neuropathic Pain

Keywords

Exercise therapy; multiple sclerosis; pain; chronic pain; neuropathic pain; non-pharmacological analgesics; resistance exercise; physical exercise; Rehabilitation; Mixed type pain

Outcome Measures

Primary Outcomes (1)

• Change in pain severity

  Subjective average pain severity over the past 7 days measured using a Numerical Rating Scale from 0 to 10 (NRS0-10)

  Intervention group: Baseline, 12 weeks post test, 24 weeks follow up test. Waitlist group: Baseline, 12 weeks post test, 24 weeks follow up/ baseline test, 36 weeks post test.

Secondary Outcomes (25)

• Change in Brief Pain Inventory (BPI)

  Intervention group: Baseline, 12 weeks post test, 24 weeks follow up test. Waitlist group: Baseline, 12 weeks post test, 24 weeks follow up/ baseline test, 36 weeks post test.

• Change in Graded Chronic Pain Scale (GCPS-R)

  Intervention group: Baseline, 12 weeks post test, 24 weeks follow up test. Waitlist group: Baseline, 12 weeks post test, 24 weeks follow up/ baseline test, 36 weeks post test.

• Change in Douleur Neuropathique 4 questions (DN4)

  Intervention group: Baseline, 12 weeks post test, 24 weeks follow up test. Waitlist group: Baseline, 12 weeks post test, 24 weeks follow up/ baseline test, 36 weeks post test.

• Change in physical activity (Baecke Habitual Physical Activity Questionnaire)

  Intervention group: Baseline, 12 weeks post test, 24 weeks follow up test. Waitlist group: Baseline, 12 weeks post test, 24 weeks follow up/ baseline test, 36 weeks post test.

• Change in Hospital Anxiety and Depression Scale (HADS)

  Intervention group: Baseline, 12 weeks post test, 24 weeks follow up test. Waitlist group: Baseline, 12 weeks post test, 24 weeks follow up/ baseline test, 36 weeks post test.

Study Arms (2)

Resistance exercise group

EXPERIMENTAL

Participants must have chronic pain (NRS ≥ 3) when enrolled and furthermore meet eligibility criteria. Intervention: 12 weeks of progressive resistance exercise followed by 12 weeks of usual care

Other: Progressive resistance exercise

Waitlist group

EXPERIMENTAL

Participants must have chronic pain (NRS ≥ 3) when enrolled and furthermore meet additional eligibility criteria. Intervention: 24 weeks of usual care followed by 12 weeks of progressive resistance exercise.

Other: Usual Care followed by progressive resistance exercise

Interventions

Progressive resistance exercise OTHER

Participants assigned to this arm will undergo 12 weeks of progressive heavy-load resistance exercise, with 5 sessions over a 2-week period (equaling a total of 30 sessions). Each session will commence with a 5-minute warm-up using a bicycle ergometer. The training program will consist of machine-based exercises, including leg press, knee extensions, hamstring curls, seated calf raises, chest press, and lateral pull-down. Progression will be ensured through an increase in the number of sets (from 3 to 4, interspersed by 1-2 minutes of rest) for each exercise along with an increment in intensity (from 15 Repetition Maximum (RM) towards 8RM.

Resistance exercise group

Usual Care followed by progressive resistance exercise OTHER

Participants assigned to this arm will undergo 24 weeks of waitlist control. The control group will continue their habitual lifestyle and usual care throughout the whole period. After 24 weeks, the waitlist control group will undergo the same progressive resistance exercise regimen as described in the intervention group.

Waitlist group

Eligibility Criteria

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

Sponsors & Collaborators

• University of Aarhus: lead
• Aalborg University: collaborator

Study Sites (1)

Aarhus University

Aarhus, Denmark, 8000, Denmark

RECRUITING

Related Publications (6)

• Rosner J, de Andrade DC, Davis KD, Gustin SM, Kramer JLK, Seal RP, Finnerup NB. Central neuropathic pain. Nat Rev Dis Primers. 2023 Dec 21;9(1):73. doi: 10.1038/s41572-023-00484-9.

  PMID: 38129427 BACKGROUND

• Heesen C, Bohm J, Reich C, Kasper J, Goebel M, Gold SM. Patient perception of bodily functions in multiple sclerosis: gait and visual function are the most valuable. Mult Scler. 2008 Aug;14(7):988-91. doi: 10.1177/1352458508088916. Epub 2008 May 27.

  PMID: 18505775 BACKGROUND

• Vaegter HB, Jones MD. Exercise-induced hypoalgesia after acute and regular exercise: experimental and clinical manifestations and possible mechanisms in individuals with and without pain. Pain Rep. 2020 Sep 23;5(5):e823. doi: 10.1097/PR9.0000000000000823. eCollection 2020 Sep-Oct.

  PMID: 33062901 BACKGROUND

• Demaneuf T, Aitken Z, Karahalios A, Leong TI, De Livera AM, Jelinek GA, Weiland TJ, Marck CH. Effectiveness of Exercise Interventions for Pain Reduction in People With Multiple Sclerosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Arch Phys Med Rehabil. 2019 Jan;100(1):128-139. doi: 10.1016/j.apmr.2018.08.178. Epub 2018 Sep 19.

  PMID: 30240593 BACKGROUND

• Yamout B, Issa Z, Herlopian A, El Bejjani M, Khalifa A, Ghadieh AS, Habib RH. Predictors of quality of life among multiple sclerosis patients: a comprehensive analysis. Eur J Neurol. 2013 May;20(5):756-64. doi: 10.1111/ene.12046. Epub 2013 Jan 8.

  PMID: 23294397 BACKGROUND

• Giordano R, Arendt-Nielsen L, Gerra MC, Kappel A, Ostergaard SE, Capriotti C, Dallabona C, Petersen KK. Pain mechanistic networks: the development using supervised multivariate data analysis and implications for chronic pain. Pain. 2025 Apr 1;166(4):847-857. doi: 10.1097/j.pain.0000000000003410. Epub 2024 Sep 18.

  PMID: 39297729 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Chronic Pain; Neuralgia; Pain; Motor Activity

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Behavior

Central Study Contacts

Rasmus C Jungersen, PhD-student

CONTACT

+4593508304; rasjun@ph.au.dk

Lars G Hvid, Associate Professor

CONTACT

93508717; lhvid@ph.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: See study description for details

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 15, 2026
• Study Start: January 15, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: January 15, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Sharing of data will commence February 2026 and is expected to terminate within a 5-year period following August 2028.
• Access Criteria: Data will be accessible exclusively to authorized personnel on encrypted servers. Data collection and data management will be conducted solely by trained staff operating under restricted access privileges.

Locations

DK (1)