Chemotherapy Induced Peripheral Neuropathy. Could Physical Therapy Help Treat Symptoms?
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|ClinicalTrials.gov Identifier: NCT02239601|
Recruitment Status : Completed
First Posted : September 15, 2014
Results First Posted : October 9, 2019
Last Update Posted : October 9, 2019
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|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Peripheral Neuropathy, Secondary to Drugs or Chemicals||Other: Physical Therapy||Not Applicable|
A common side effect is chemotherapy induced peripheral neuropathy (CIPN). CIPN is a small fibre sensory neuropathy that develops in the hands/feet and worsens with increasing dose and duration of treatment. It impacts the Aβ, Aδ, and C-Fiber function involved in light touch and vibration sense, thermal detection and thermal pain. This results in a variety of positive and/or negative sensory symptoms including hypoesthesia, dysesthesias, hyperalgesia, allodynia and neuropathic pain. Quantitative sensory testing (QST) are a variety of non-invasive tests aimed at quantifying sensory perceptions used in research to clinically assess neuropathy. It is used for sensory detection and pain thresholds for both mechanical and thermal stimuli. QST provides information on large myelinated (Aβ), small thinly myelinated (Aδ) and unmyelinated (C-fiber) function or dysfunction. Deep pressure threshold measured by a pressure algometry stimulates intramuscular afferents, and can be used as a measure of central sensitization when used at a distant site from the site of pain. Aδ fibres transmit cool detection threshold, while warm detection threshold is transmitted by C-fibers. Both noxious heat and noxious cold transmit via C-fiber and Aδ fibers. An increased sensitivity to thermal pain thresholds, results in thermal hyperalgesia.
Physical therapy treatment for nerve disorders is well established in orthopedics and plastic surgery for entrapment neuropathies, neuropathic pain, post-operative nerve repair and regeneration. Nerve gliding exercises are frequently used exercises in physical therapy to improve neural excursion across joints, improve pain and decrease inflammation. Patient reported symptoms (patient questionnaires NPRS, S-LANSS and DASH) and quantitative sensory testing (QST) specifically pain pressure thresholds and vibration were used for the primary purpose in evaluating the role for an upper extremity nerve mobilization physical therapy home program during chemotherapy for the prevention and management of CIPN.
Primary Outcome Measures was the NPRS and reported as those having no vs no pain. Grip strength, Vibration, DASH and S-LANSS were identified outcome measures prior to the trial that would best describe sensory impairment and function for the physical therapy question
Additional QST measures collected included warm/cool, Hot/Cold Pain thresholds that were used with the vibration data to compare quantitative data on the right and left side to evaluate possible a possible dual nerve disorder when combined with surgery as well as identifying different sensory profiles of QST data between those reporting neuropathic pain and non-neuropathic pain using the S-LANSS
A sub analysis of data was completed dividing participants that remained active throughout compared to less active participants to evaluate the effect of exercise on sensory preservation. This was not an intended analysis at the beginning of the trial and these participants were not randomized.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||61 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Chemotherapy - Induced Peripheral Neuropathy (CIPN). Could There be a Role for Physical Therapy Treatment?|
|Actual Study Start Date :||December 1, 2014|
|Actual Primary Completion Date :||November 1, 2017|
|Actual Study Completion Date :||November 2017|
Experimental: Physical Therapy
4 Physical therapy treatment sessions provided prior to chemotherapy and a home program to continue throughout the trial.
Other: Physical Therapy
Physical therapy assessment and treatment for any positive signs of nerve entrapment prior to chemotherapy including nerve gliding exercises, education and splinting. A home program was provided and continued throughout chemotherapy treatment
Other Name: physiotherapy
- Percentage of Participants With 'Pain' or 'no Pain' as Measured by the Numeric Pain Rating Scale [ Time Frame: Regression models of pain reported over time (mid-docetaxel chemotherapy- 6 months post-chemotherapy). Mid-chemotherapy time frame participants were re-assessed after the 2 round of TC and 4th round of FECD. ]Numeric Pain Rating Scale - pain rating scale 0-10 (0= no pain to 10= most pain imaginable). Reported as percentages of participants with pain (1-10) vs no pain (0)
- Disability of the Arm, Shoulder and Hand (DASH) [ Time Frame: administered on each re-assessment (pre-chemotherapy, mid-way through docetaxel chemotherapy, end of chemotherapy, 6 months post-chemotherapy) and mixed models accounted for all time points ]A 30 item participant reported questionnaire commonly used to gauge upper limb function. Each item is scored 1-5 with 1 being 'no difficulty' and 5 being 'unable'. Overall score calculated as: [average response (sum of responses divided by number of responses) -1] x 25 to give a score out of 100. Minimum score is 30 with a maximum score of 150. The DASH was chosen because of high test-retest reliability and the responsiveness and construct validity in patients with breast cancer over other quality of life measures. A minimal clinical important difference is a change score of 15. Higher score indicates more impairment to the upper limb
- Percentage of Participants With Neuropathic Pain Defined by the Self Report Version of Leeds Assessment for Neuropathic Symptoms and Signs (S-LANSS). [ Time Frame: administered on each re-assessment (Visit 1 - pre-chemotherapy, Visit 2 - half-way through chemotherapy, Visit 3 - end of chemotherapy, Visit 4 - 3 months post-chemotherapy) and mixed models accounted for all time points ]a 7 item patient reported questionnaire and was used to confirm the presence of neuropathic pain. The score ranges from 0-19 (no symptoms=0, sever symptoms=19) with a score above 12 indicative of neuropathic pain/symptoms. S-LANSS was chosen because of its' specificity and accuracy in a cancer population. Participants were requested to answer specifically for the hands, not feet.
- Vibration Sensory Analysis [ Time Frame: administered on each re-assessment (Visit 1 - pre-chemotherapy, Visit 2 - half-way through chemotherapy, Visit 3 - end of chemotherapy, Visit 4 - 6 months post-chemotherapy) and mixed models accounted for all time points ]Vibration analysis testing for perception thresholds are specific to Aβ nerve fibres. The TSAII Vibration Sensory Analyzer (VSA): Medoc, Israel, was used. The pulp of the index finger lightly touches the sensor that delivers random and varying vibration amplitudes (µm). The participant responds "yes/no" to sensing the vibration. Vibration perception was selected for its sensitivity and has been suggested to be the first clinical sign of CIPN symptoms and was tested bilaterally. Low score indicates better perception while a higher score is poorer sensation. Perception score reported in micrometers (up to 4cm)
- Pain Pressure Thresholds [ Time Frame: administered on each re-assessment (Visit 1 - pre-chemotherapy, Visit 2 - half-way through chemotherapy, Visit 3 - end of chemotherapy, Visit 4 - 6 months post-chemotherapy) and mixed models accounted for all time points ]Pressure Algometry (Somedic AB, Sweden) measured pressure/pain thresholds. A hand-held device applied perpendicular to the muscles being tested. Increasing pressure is applied until the participant determines that the sensation has changed from a feeling of pressure to a feeling of pain and force (Kpa) is recorded. When tested at a distant site from the source of pain this test measures central sensitization. Lower pressure values (more sensitive to noxious stimuli) suggest impaired central pain and/or diminished descending inhibition pathway. The left quadriceps muscle was tested as a measure of central sensitization.
- Grip Strength [ Time Frame: administered on each re-assessment (Visit 1 - pre-chemotherapy, Visit 2 - half-way through chemotherapy, Visit 3 - end of chemotherapy, Visit 4 - 6 months post-chemotherapy) and mixed models accounted for all time points ]Hand Dynamometry records grip strength in kgs and was used as a measure of function (3 trials). The dominant hand was tested using the Jamar dynamometer (Patterson medical, USA) in the 2nd handle position. All 48 participants were right handed.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients diagnosed with stage I-III breast cancer undergoing regular docetaxel treatment either docetaxel-cyclophosphamide (TC) or 5FU-epirubicin-cyclophosphamide-docetaxel (FEC-D).
- Patients that have not had chemotherapy in the past and do not have identified risk factors (listed below in the exclusion criteria).
- All patients must be able to communicate in english or be able to have a translator present at all appointments.
- Patients diagnosed with stage IV breast cancer or who have co-morbid conditions that are known to cause peripheral neuropathic symptoms, including previous chemotherapy, exposure to toxins (such as lead), Diabetes, Shingles, B12 deficiency, Alcoholism, Lyme disease, Syphilis, HIV, Hereditary disorders such as Charcot-Marie Tooth.
- Patients not planned to receive Docetaxel therapy.
- Patients who cannot communicate in English and unable to bring an interpreter will also be excluded.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02239601
|Rehabilitation Hospital, Health Sciences Centre, 800 Sherbrook St|
|Winnipeg, Manitoba, Canada, R3A 1M4|
|Study Director:||Barbara L Shay, PhD||University of Manitoba|
|Principal Investigator:||Elizabeth R Hammond, PhD||University of Manitoba|
Documents provided by Dr. Marshall Pitz, CancerCare Manitoba:
|Responsible Party:||Dr. Marshall Pitz, Medical Oncologist and Associate Professor , University of Manitoba, CancerCare Manitoba|
|Other Study ID Numbers:||
|First Posted:||September 15, 2014 Key Record Dates|
|Results First Posted:||October 9, 2019|
|Last Update Posted:||October 9, 2019|
|Last Verified:||September 2019|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
Chemotherapy Induced Peripheral Neuropathy (CIPN)
Nerve gliding exercises
Peripheral Nervous System Diseases
Nervous System Diseases