Exercise Rehabilitation for Peripheral Neuropathy

(EX-CIPN Trial)

Overseen By Eric Antonen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must not be taking: Ado-trastuzumab emtansine

Disqualifiers: Neurological conditions, Pre-existing neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 10 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if the EX-CIPN exercise-based intervention is feasible, acceptable, and safe in participants with persistent chemotherapy-induced peripheral neuropathy (CIPN). It will also give insight on the effectiveness of the exercise intervention in treating CIPN symptoms. The main questions it aims to answer are: * Is EX-CIPN safe, acceptable, and feasible in cancer survivors experiencing persistent CIPN? * Are the study design and methods feasible (recruitment and retention rates, feasibility of data collection and procedures)? Researchers will provide all participants with the exercise-based intervention. Participants will: * Complete assessments at baseline, immediately post-intervention, and 3-months post-intervention * Complete a 10-week remote, individualized exercise program * Receive health coaching calls on weeks 2, 3, 4, 6, and 8 of the intervention * Wear a FitBit throughout the study to track physical activity and promote behaviour change

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking ado-trastuzumab emtansine (TDM1).

What data supports the effectiveness of the treatment EX-CIPN for peripheral neuropathy?

Research shows that exercise therapy can improve symptoms and physical function in people with diabetic neuropathy, and specific exercise regimens can enhance balance and confidence in those with peripheral neuropathy. Additionally, tai chi, a form of exercise, has been found to increase strength, balance, and stamina in older adults with peripheral neuropathy. ^{1 2 3 4 5}

Is exercise rehabilitation safe for people with peripheral neuropathy?

Research on exercise-based rehabilitation for chemotherapy-induced peripheral neuropathy suggests it is generally safe for humans, as it is often included in integrated programs with other therapies like massage and passive mobilization. ^{6 7 8 9 10}

How is the EX-CIPN treatment different from other treatments for peripheral neuropathy?

EX-CIPN is unique because it focuses on exercise-based rehabilitation to manage peripheral neuropathy, which is different from traditional drug treatments. It aims to improve strength, stamina, and sensation through physical activity, offering a non-drug approach to reduce symptoms and enhance quality of life. ^{1 2 4 6 11}

Eligibility Criteria

This trial is for cancer survivors who are dealing with persistent chemotherapy-induced peripheral neuropathy (CIPN). Participants should be willing to engage in a 10-week exercise program, receive health coaching calls, and wear a FitBit. Specific eligibility criteria were not provided.

Inclusion Criteria

Currently engaging in < 90min per week of planned moderate-intensity aerobic exercise

I finished chemotherapy more than 6 months ago.

I have nerve damage from chemotherapy.

Exclusion Criteria

Currently enrolled in other cancer rehabilitation or exercise-based programs/interventions

I am currently on Kadcyla (TDM1) treatment.

I had nerve damage before starting chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants complete a 10-week remote, individualized exercise program with health coaching calls and Fitbit monitoring

10 weeks

5 health coaching calls (weeks 2, 3, 4, 6, and 8)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at baseline, immediately post-intervention, and 3-months post-intervention

14 weeks

3 assessment visits (baseline, post-intervention, 3-months post-intervention)

Treatment Details

Interventions

• EX-CIPN

Trial Overview The EX-CIPN intervention being tested involves an individualized exercise program designed to treat symptoms of CIPN. The study will assess the safety, acceptability, and feasibility of this approach through participant assessments at various stages.

Participant Groups

Group I: EX-CIPN Exercise- Based intervention Experimental Treatment 1 Intervention

This arm is provided with an intervention that includes an individualized exercise program, remote monitoring, and remote person-to-person clinical support.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Exercise therapy may provide short-term benefits in reducing neuropathic symptoms and improving physical function in people with diabetic neuropathy, based on a review of 11 randomized clinical trials involving 517 participants.

However, the overall quality of evidence supporting these benefits is very low, and no significant effects were observed on psychosocial aspects of health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise therapy on diabetic neuropathy: A systematic review and meta-analysis. Hernando-Garijo, I., Medrano-de-la-Fuente, R., Mingo-Gómez, MT., et al.[2023]

The study involved 10 adults with diabetic peripheral neuropathy (DPN) who participated in a 4-week intervention aimed at promoting physical activity self-management, which included exercise tasters and behavior change counseling.

Participants experienced significant reductions in foot symptoms, specifically aching and burning pain, after the intervention, with no major adverse events reported, indicating that the Physical Activity Intelligence (PAI) self-monitoring approach is both safe and potentially effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personal Activity Intelligence eHealth intervention in people with diabetic peripheral neuropathy: A feasibility study. Coombes, BK., Bisset, LM., Sierra-Silvestre, E., et al.[2023]

A 12-week tai chi program led to long-term engagement in exercise for older adults with peripheral neuropathy, with participants continuing classes for an additional 18 months, highlighting the importance of psychosocial support in maintaining exercise routines.

Participants showed significant improvements in strength, balance, and stamina, confirming the physical benefits of tai chi, although changes in quality of life scores were not statistically significant, qualitative feedback indicated meaningful improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Tai Chi on Peripheral Neuropathy Revisited: A Mixed-Methods Study. Hermanns, M., Haas, BK., Rath, L., et al.[2020]

A 12-week integrated exercise program significantly improved glycemic control and peripheral sensation in patients with Type 2 diabetic peripheral neuropathy, as indicated by better results in various measures like HbA1c and sensory tests.

The exercise program included techniques like massage and foam rolling to enhance blood circulation and reduce pain, which likely facilitated the patients' ability to engage in aerobic and resistance exercises more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated Exercise and Glycemic and Peripheral Sensation Control in Diabetic Neuropathy: A Single-Blind, Randomized Controlled Trial. Heidari, M., Zolaktaf, V., Ghasemi, G., et al.[2022]

A 3-week specific exercise regimen significantly improved balance measures in 10 subjects with diabetic peripheral neuropathy, compared to a control group, indicating its potential efficacy for enhancing postural stability.

While the intervention also showed a trend towards improved confidence in balance (measured by the ABC scale), further research is needed to see if these improvements lead to a reduced risk of falls in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy. Richardson, JK., Sandman, D., Vela, S.[2022]

Exercise significantly reduces the severity of chemotherapy-induced peripheral neuropathy (CIPN) symptoms and improves peripheral deep sensitivity, based on a meta-analysis of 13 studies.

Sensoriomotor training and mind-body exercises are particularly effective in alleviating CIPN symptoms, while active nerve-specific and mind-body exercises enhance peripheral deep sensitivity in cancer patients and survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise interventions to reduce chemotherapy-induced peripheral neuropathy severity: A meta-analysis. Nuñez de Arenas-Arroyo, S., Cavero-Redondo, I., Torres-Costoso, A., et al.[2023]

An 8-week multimodal exercise intervention significantly improved symptoms of chemotherapy-induced peripheral neuropathy (CIPN) in 29 cancer survivors, enhancing balance, mobility, and quality of life without affecting neurophysiologic parameters.

The study suggests that exercise can be a beneficial rehabilitation strategy for CIPN, warranting further large-scale trials to confirm these findings and explore the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise-based rehabilitation for cancer survivors with chemotherapy-induced peripheral neuropathy. McCrary, JM., Goldstein, D., Sandler, CX., et al.[2021]

In a study involving 131 patients with chemotherapy-induced polyneuropathy (CIPN), whole-body vibration (WBV) combined with an integrated program (IP) showed a significant reduction in the time needed for the chair-rising test, indicating improved physical fitness and coordination compared to standard treatment alone.

All patients reported less pain and symptoms over time, with both treatment groups showing improvement, but WBV specifically enhanced warm-detection-threshold, suggesting it may have additional benefits for sensory function in CIPN patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized exploratory phase 2 study in patients with chemotherapy-related peripheral neuropathy evaluating whole-body vibration training as adjunct to an integrated program including massage, passive mobilization and physical exercises. Schönsteiner, SS., Bauder Mißbach, H., Benner, A., et al.[2020]

This pilot study will assess the effectiveness of home-based high-tone external muscle stimulation (HTEMS) therapy in improving symptoms of chemotherapy-induced peripheral neuropathy (CIPN) in 50 patients over 8 weeks, using a randomized controlled design.

The primary outcome will be measured using the EORTC QLQ-CIPN 20 questionnaire, with secondary outcomes including changes in health-related quality of life and various sensory and strength assessments, aiming to identify a potentially novel treatment for CIPN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of high tone therapy and transcutaneous electrical nerve stimulation therapy in chemotherapy-induced polyneuropathy. Schaffler-Schaden, D., Sassmann, R., Johansson, T., et al.[2020]

Scrambler therapy (ST) significantly reduced pain levels in adolescents with chemotherapy-induced peripheral neuropathy (CIPN), with pain scores dropping from an average of 9.22 to 0.11 after treatment, indicating strong efficacy.

The therapy also improved quality of life across multiple areas, including general activity, mood, walking ability, sleep, and social relationships, with no reported side effects, suggesting it is a safe and effective option for managing CIPN in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study. Tomasello, C., Pinto, RM., Mennini, C., et al.[2019]

The review found inadequate evidence to determine the overall effect of exercise therapy on functional ability in people with peripheral neuropathy, as only one trial fully met the inclusion criteria and results could not be pooled due to variability.

However, there is some indication that progressive resisted exercise may moderately improve muscle strength in the affected muscles of individuals with peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise for people with peripheral neuropathy. White, CM., Pritchard, J., Turner-Stokes, L.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of exercise therapy on diabetic neuropathy: A systematic review and meta-analysis. [2023]

2. Australia pubmed.ncbi.nlm.nih.gov

Personal Activity Intelligence eHealth intervention in people with diabetic peripheral neuropathy: A feasibility study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Impact of Tai Chi on Peripheral Neuropathy Revisited: A Mixed-Methods Study. [2020]

4. Iran pubmed.ncbi.nlm.nih.gov

Integrated Exercise and Glycemic and Peripheral Sensation Control in Diabetic Neuropathy: A Single-Blind, Randomized Controlled Trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy. [2022]

6. Denmark pubmed.ncbi.nlm.nih.gov

Effects of exercise interventions to reduce chemotherapy-induced peripheral neuropathy severity: A meta-analysis. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Exercise-based rehabilitation for cancer survivors with chemotherapy-induced peripheral neuropathy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

A randomized exploratory phase 2 study in patients with chemotherapy-related peripheral neuropathy evaluating whole-body vibration training as adjunct to an integrated program including massage, passive mobilization and physical exercises. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Comparison of high tone therapy and transcutaneous electrical nerve stimulation therapy in chemotherapy-induced polyneuropathy. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy-induced peripheral neuropathy in adolescents: A preliminary study. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Exercise for people with peripheral neuropathy. [2022]