Clinical trial NCT02239601: Chemotherapy Induced Peripheral Neuropathy. Could Physical Therapy Help Treat Symptoms?
Official title: Chemotherapy - Induced Peripheral Neuropathy (CIPN). Could There be a Role for Physical Therapy Treatment?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Peripheral Neuropathy, Secondary to Drugs or Chemicals
Keywords: Physical Therapy
Physiotherapy
Breast Cancer
Chemotherapy Induced Peripheral Neuropathy (CIPN)
Nerve gliding exercises
Nerve Entrapment
Lead sponsor: CancerCare Manitoba
Sponsor class: OTHER
Collaborators: name: University of Manitoba
First posted: 2014-09-15
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The cause of Chemotherapy-Induced Peripheral Neuropathy (CIPN) is still unknown. An estimated 55-60% of patients will experience lasting symptoms affecting function for years post-treatment. Physical therapy is an established, effective treatment for entrapped nerves and neuropathic pain. This study sought to identify additional risk factors and provide evidence for the role of physical therapy in the treatment of CIPN.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of Participants With 'Pain' or 'no Pain' as Measured by the Numeric Pain Rating Scale
timeFrame: 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.
measure: Disability of the Arm, Shoulder and Hand (DASH)
timeFrame: 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
measure: Percentage of Participants With Neuropathic Pain Defined by the Self Report Version of Leeds Assessment for Neuropathic Symptoms and Signs (S-LANSS).
timeFrame: 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
Secondary outcomes:
measure: Vibration Sensory Analysis
timeFrame: 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
measure: Pain Pressure Thresholds
timeFrame: 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
measure: Grip Strength
timeFrame: 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
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Rehabilitation Hospital, Health Sciences Centre, 800 Sherbrook St
state: Manitoba
Study officials:
affiliation: University of Manitoba
name: Barbara L Shay, PhD
role: STUDY_DIRECTOR
affiliation: University of Manitoba
name: Elizabeth R Hammond, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andersen Hammond E, Pitz M, Steinfeld K, Lambert P, Shay B. An Exploratory Randomized Trial of Physical Therapy for the Treatment of Chemotherapy-Induced Peripheral Neuropathy. Neurorehabil Neural Repair. 2020 Mar;34(3):235-246. doi: 10.1177/1545968319899918. Epub 2020 Jan 24.