Effect of Resistance and Aerobic Exercise in CIDP or MMN

Study Overview
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Brief Summary
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Resistance and aerobic exercise has been shown to be effective for maintenance of muscle strength in patients with neuromuscular diseases. Exercise in CIDP and MMN is sparsely described. The aim of the study is to evaluate changes in muscle strength during high intensive resistance training and changes in maximal oxygen consumption (VO2-max) during high intensive aerobic training in patients with CIDP or MMN in maintenance therapy with subcutaneous immunoglobulin. The hypotheses are that muscle strength and VO2-max are significantly increased during the training sessions.

Official Title
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Effect of Resistance and Aerobic Exercise on Muscle Strength, Aerobic Capacity and Quality of Life in Patients Treated With Immunoglobulin for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or Multifocal Motor Neuropathy (MMN)

Conditions
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Chronic Inflammatory Demyelinating Polyneuropathy, Multifocal Motor Neuropathy

Intervention / Treatment
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* Other: Resistance training
* Other: Aerobic training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 and < 80 years Diagnosed with definite or probable CIDP or definite or probable MMN fulfilling the European Federation of Neurological Sciences/Peripheral Nerve Society (EFNS/PNS) criteria Stable maintenance therapy with immunoglobulin (no change of dosage < 3 months before inclusion) Duration of CIDP or MMN > 6 months Negative result on a pregnancy test (HCG-based assay in urine) for women of childbearing potential and use of a reliable method of contraception for the duration of the study Exclusion Criteria: Other cause of neuropathy (incl. pressure neuropathy) Exercise before enrolment (> 1 hour of exercise per week or > 4 km bicycling per day) Walking distance < 10 meter with or without aid Diabetes mellitus, severe cardiac or pulmonary disease, malignancies Known history of adverse reactions to Immunoglobulin A in other products Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products. History of malignancies of lymphoid cells and immunodeficiency with lymphoma Known liver function impairment (ALAT 3 times above upper limit of normal) Known protein-losing enteropathies or proteinuria. Known of renal function impairment (creatinine >120 micromol/L or creatinine >1.35 mg/dL), or predisposition for acute renal failure (e.g., any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs). Treatment with any investigational medicinal product within 3 months prior to first infusion of Gammanorm Known or suspected HIV, Hepatitis Virus C or B infection Pregnant or nursing women Planned pregnancy during course of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Run-in - Aerobic - Resistance<br>Week -12 to 0: Run-in period with no training Week 0 to 12: Aerobic training on ergometer bicycle Week 12 to 24: Resistance training with dumbbells | Other: Resistance training<br>* Participants do resistance training of selected muscle groups. Resistance are predefined from 1-repetition max (1-RM) and increased during the 12 weeks of training: Week 0-4: 70-80 % of 1-RM Week 5-8: 75-86 % of 1-RM Week 9-12: 80-92% of 1-RM Participants trains unilateral, the opposite site serves as reference. MMN patients train elbow (flexion/extension) and wrist (flexion/extension) CIDP patients train knee (flexion/extension) and elbow (flexion/extension)<br>Other: Aerobic training<br>* Participants train on ergometer bicycle 2 times weekly increasing during the first weeks to 3 times weekly. Workload is measured before initiation and VO2-max, heart rate and blood pressure will be measured as well. Patients train with 60-75 % of VO2-max for 30 minutes per training session. They use heart rate monitor to store data.<br>|
| Experimental: Run-in - Resistance - Aerobic<br>Week -12 to 0: Run-in period with no training Week 0 to 12: Resistance training with dumbbells Week 12 to 24: Aerobic training on ergometer bicycle | Other: Resistance training<br>* Participants do resistance training of selected muscle groups. Resistance are predefined from 1-repetition max (1-RM) and increased during the 12 weeks of training: Week 0-4: 70-80 % of 1-RM Week 5-8: 75-86 % of 1-RM Week 9-12: 80-92% of 1-RM Participants trains unilateral, the opposite site serves as reference. MMN patients train elbow (flexion/extension) and wrist (flexion/extension) CIDP patients train knee (flexion/extension) and elbow (flexion/extension)<br>Other: Aerobic training<br>* Participants train on ergometer bicycle 2 times weekly increasing during the first weeks to 3 times weekly. Workload is measured before initiation and VO2-max, heart rate and blood pressure will be measured as well. Patients train with 60-75 % of VO2-max for 30 minutes per training session. They use heart rate monitor to store data.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in isokinetic muscle strength | Changes in isokinetic muscle strength during resistance exercise. Four muscle groups bilateral are selected. CIDP: Knee flexion/extension Elbow flexion/extension MMN: Elbow flexion/extension Wrist flexion/extension | -12, 0, 6, 12 weeks or -12, 0, 12, 18, 24 weeks | 
| Changes in maximal oxygen consumption (VO2-max) | VO2-max are measured during the 12 weeks aerobic exercise session and at enrolment 12 weeks before start of exercise. VO2-max are measured while the participant running on a ergometer bicycle by accumulation of exhaled air | -12, 0, 6, 12 weeks or -12, 0, 12, 18, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Medical Research Council (MRC) |  | -12, 0, 6, 12, 18, 24 weeks | 
| Change in Overall Disability Sum Score (ODSS) |  | -12, 0, 6, 12, 18, 24 weeks | 
| Change in 6-Minute Walk test |  | -12, 0, 6, 12 weeks or -12, 0, 12, 18, 24 weeks | 
| Change in Quality of Life measured by The Short Form (36) Health Survey (SF-36) questionnaire |  | -12, 0, 6, 12, 18, 24 weeks | 
| Change in Fatigue Severity Score (FSS) |  | -12, 0, 6, 12, 18, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subcutaneous immunoglobulin, Resistance training, Aerobic exercise, Isokinetic muscle strength, Bicycle ergometry test