CIPN - Chemotherapy-Induced Peripheral Neuropathy
Conditions
Keywords
Neuropathy, CIPN, Cryotherapy, Compression therapy
Brief summary
The primary objective of this study is to select the best intervention from cold therapy, compression therapy and placebo at reducing neuropathic pain as measured by the change in the Neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) - Taxane questionnaire, following 12 weeks of neoadjuvant/adjuvant chemotherapy with paclitaxel or docetaxel among breast cancer patients.
Detailed description
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent side effect resulting from the administration of cytotoxic chemotherapeutic agents. The incidence of CIPN can vary on the type of agent used, the frequency with which it is given, and the cumulative dose. Unfortunately, for some patients, symptoms may persist even after discontinuation of the drug due to irreversible nerve damage. As of now, there are no established agents for CIPN prevention. This is a randomized, placebo-controlled clinical selection trial of interventions for CIPN in patients treated with docetaxel every 3 weeks or paclitaxel on a weekly schedule. Patients will be randomly assigned to receive either frozen gloves and socks, compression gloves and socks, or loose gloves and socks (placebo arm) during chemotherapy infusion to study the best intervention at reducing neuropathic pain.
Interventions
DEVICECryotherapy
Study subjects will wear NatraCure flexible socks on bilateral hands and feet. The sock will act as a mitten and covers the entire hand until past the wrist. There are 2 gel packs inserted into the sock, to provide cooling to the dorsal and frontal aspect of the hand. For the feet, the sock will cover the entire foot until above the ankle. Garments will be refrigerated for at least 3 hours at -25 to -30 Celsius prior to use. With each infusion, patients will wear the frozen garments on their hands and feet for a total of 90-120 minutes, beginning 15 minutes before the start of the infusion and until 15 minutes after the end of the infusion. Two sets of socks will be used during each session for 45-60 minutes each to maintain a consistently low temperatures of the extremities.
DEVICECompression Therapy
Study participants will wear Sigvaris Secure Arm Sleeves and Gloves on bilateral upper extremities. The sleeves and gloves provide 20-30mmHg of compression. Subjects will wear Sigvaris CompreFlex Lite compression garments on the lower extremities which includes a transition liner with a compressive foot, providing 20-30mmHg of compression on the lower leg and 15mmHg on the toes and feet. AccuTabs will be placed along the CompreFlex Lite to easily and accurately set the compression level at 20-30mmHg. With each chemotherapy infusion, patients will wear the sleeves/gloves and socks for a total of 90-120 minutes, beginning 15 minutes before the start of the infusion and until 15 minutes after the end of the infusion.
DEVICELoose glove/sock
Study participants will wear a non-compressive sleeve and loosely fitting glove on bilateral arms and hands. They will also wear a non-compressive Sigvaris Basic Liner with the CompreFlex Lite loosely applied over it. The investigators will verify that no compression is applied via using an interface pressure sensor (PicoPress). The maximum level of allowed pressure for garments will be 3mmHg. If the pressure reading is greater than 3mmHg, then a larger garment size will be used. Measurements with the pressure sensor will be repeated as needed to ensure a low pressure level of less than 3mmHg. With each chemotherapy infusion, patients will wear the gloves and socks for a total of 90-120 minutes, beginning 15 minutes before the start of the infusion and until 15 minutes after the end of the infusion.
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
The preferred intervention can be selected during the ongoing enrollment as soon as the pre-specified selection criteria are met, and further enrollment will cease.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Age greater or equal to 18 years. * History of stage I-III breast cancer * Patient scheduled to be receiving adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks * Signed informed consent * Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%,)
Exclusion criteria
* Prior treatment with taxane or platinum based chemotherapy * Known history of neuropathy * Raynaud's phenomenon * Peripheral arterial ischemia * Cold intolerance * Current use of duloxetine which may mitigate chemotherapy-induced peripheral neuropathy (CIPN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Successful Outcomes (<5-point Decrease in FACT-NTX From Baseline) | Baseline, 12 weeks | The primary endpoint is the change in FACT NTX at 12 weeks from the start of chemotherapy. The change in FACT NTX will be dichotomized into a good outcome (change in FACT NTX less than 5 from baseline to week 12) versus a poor outcome (change in FACT NTX greater than or equal to 5 from baseline to week 12). The FACT-NTX subscale includes 11 items, each of which is divided into 5 scoring levels: 0, 1, 2, 3, 4, and a total score of 44. The scale is graded 0-4. A low score indicates a good effect. This change in FACT-NTX scale score indicates the proportion of patients with successful outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nail Toxicity | Baseline, 12 weeks, 24 weeks | The number of participants with a change in cutaneous toxicity and onycholysis will be assessed by a healthcare professional using the National Cancer Institute Common Toxicity Criteria (Version 2), specifically nail changes. Grade 1 includes discoloration, ridging (koilonychia), or pitting of the nails and Grade 2 is partial or complete loss of nail(s) or pain in the nail beds. A higher grade indicates more nail toxicity. |
| Comfort With Intervention Scale Score | Up to 24 weeks | Comfort with the study intervention will be assessed on a 4-point scale, (0=dissatisfied; 1=not satisfied; 2=satisfied; 3=very satisfied) with 3 indicating a better outcome. |
| Vibration Perception and Disappearance Threshold | Up to 24 weeks | Study participants will be assessed for development of sensory neurological dysfunction. Vibration perception will be assessed using a tuning fork. Vibration threshold will be tested on the bilateral dorsum of the distal interphalangeal joint of the index finger and dorsum of the interphalangeal joint of the hallux. Subjects will be asked to indicate when the vibration stimulus is initially felt (perception threshold) and when the stimulus disappears (disappearance threshold.) The vibration perception threshold is the average of three paired measurements. |
| Change in NCI-CTCAE Grade for CIPN | Baseline, 12, and 24 weeks | National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) is a subjective method to evaluate CIPN which is performed by a healthcare professional. The patient's peripheral sensory neuropathy, peripheral motor neuropathy, dysesthesia, paresthesia and neuralgia will be graded on a scale of 1 to 5 depending on severity with 1 indicating a better outcome. |
| Average Time to Complete 'Timed Get up and go' Test | Up to 24 weeks | The 'timed get up and go' test is a rapid and widely used clinical performance-based measure of lower extremity function, mobility, and fall risk. Subjects are asked to stand up from a standard chair (seat height between 44 and 47 cm), walk a distance of 3 m (marked on the floor) at a comfortable pace, turn, walk back and sit down. Time will be measured in seconds. Shorter times indicate better performance. |
| Tandem and Unipedal Stance Test | Up to 24 weeks | Balance will be assessed using the tandem and unipedal stance test. In this assessment, the subject stands with one foot in front of the other (heel to toe) (30 seconds), then on one leg with: eyes open (60 seconds), eyes closed (30 seconds), and eyes open with head rotation (30 seconds) with arms held comfortably at the side. The test was accepted failure when the stance foot shifted in any way or the nonstance foot touched the ground. Tests are recorded as achieved (yes) or not achieved (no). |
| Adherence to Study Intervention | Up to 24 weeks | The number of participants who adhered to the intervention. Adherence is defined as wearing the assigned gloves and socks for greater than or equal to 80% of infusions. |
| Subjects Perceived Pain and Pressure Using Neuropen Test | Up to 24 weeks | Evaluation of other sensory endpoints including touch, pressure and pain will be evaluated using a Neuropen. Touch and pressure sensation will be assessed using a 10-g monofilament on the subject's dominant foot. Pain and subjective sharpness sensation will be assessed using the Neuropen on the dominant foot. The spring mechanism is calibrated to exert a force of 40 grams to help identify subjects with loss of pain sensation. Ten points on the foot are tested. If the participant detects pain and pressure on less than 8 points, pain and pressure perception are considered diminished. Perception on 8 points of the foot or greater is considered a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cryotherapy Men or women over the age of 18 with a history of stage I-III breast cancer and is scheduled to receive adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks.
Cryotherapy: Study subjects will wear NatraCure flexible socks on bilateral hands and feet. The sock will act as a mitten and covers the entire hand until past the wrist. There are 2 gel packs inserted into the sock, to provide cooling to the dorsal and frontal aspect of the hand. For the feet, the sock will cover the entire foot until above the ankle. Garments will be refrigerated for at least 3 hours at -25 to -30 Celsius prior to use. With each infusion, patients will wear the frozen garments on their hands and feet for a total of 90-120 minutes, beginning 15 minutes before the start of the infusion and until 15 minutes after the end of the infusion. Two sets of socks will be used during each session for 45-60 minutes each to maintain a consistently low temperatures of the extremities. | 20 |
| Compression Therapy Men or women over the age of 18 with a history of stage I-III breast cancer and is scheduled to receive adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks.
Compression Therapy: Study participants will wear Sigvaris Secure Arm Sleeves and Gloves on bilateral upper extremities. The sleeves and gloves provide 20-30mmHg of compression. Subjects will wear Sigvaris CompreFlex Lite compression garments on the lower extremities which includes a transition liner with a compressive foot, providing 20-30mmHg of compression on the lower leg and 15mmHg on the toes and feet. AccuTabs will be placed along the CompreFlex Lite to easily and accurately set the compression level at 20-30mmHg. With each chemotherapy infusion, patients will wear the sleeves/gloves and socks for a total of 90-120 minutes, beginning 15 minutes before the start of the infusion and until 15 minutes after the end of the infusion. | 22 |
| Control Arm (Loose Glove/Sock) Men or women over the age of 18 with a history of stage I-III breast cancer and is scheduled to receive adjuvant or neoadjuvant paclitaxel or docetaxel for at least 12 weeks.
Loose glove/sock: Study participants will wear a non-compressive sleeve and loosely fitting glove on bilateral arms and hands. They will also wear a non-compressive Sigvaris Basic Liner with the CompreFlex Lite loosely applied over it. The investigators will verify that no compression is applied via using an interface pressure sensor (PicoPress). The maximum level of allowed pressure for garments will be 3mmHg. If the pressure reading is greater than 3mmHg, then a larger garment size will be used. Measurements with the pressure sensor will be repeated as needed to ensure a low pressure level of less than 3mmHg. With each chemotherapy infusion, patients will wear the gloves and socks for a total of 90-120 minutes, beginning 15 minutes before the start of the infusion and until 15 minutes after the end of the infusion. | 21 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Cryotherapy | Compression Therapy | Control Arm (Loose Glove/Sock) | Total |
|---|---|---|---|---|
| Age, Continuous | 58.5 years | 53.5 years | 51.0 years | 53.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 9 Participants | 8 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 10 Participants | 10 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Number docetaxel of treatments before baseline | 5.1 treatments STANDARD_DEVIATION 1.3 | 5.5 treatments STANDARD_DEVIATION 0.9 | 4.8 treatments STANDARD_DEVIATION 1.7 | 5.1 treatments STANDARD_DEVIATION 1.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 4 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 7 Participants | 5 Participants | 21 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Female | 20 Participants | 22 Participants | 21 Participants | 63 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 2 / 22 | 1 / 21 |
| other Total, other adverse events | 16 / 20 | 20 / 22 | 19 / 21 |
| serious Total, serious adverse events | 3 / 20 | 3 / 22 | 1 / 21 |
Outcome results
Primary
Proportion of Patients With Successful Outcomes (<5-point Decrease in FACT-NTX From Baseline)
The primary endpoint is the change in FACT NTX at 12 weeks from the start of chemotherapy. The change in FACT NTX will be dichotomized into a good outcome (change in FACT NTX less than 5 from baseline to week 12) versus a poor outcome (change in FACT NTX greater than or equal to 5 from baseline to week 12). The FACT-NTX subscale includes 11 items, each of which is divided into 5 scoring levels: 0, 1, 2, 3, 4, and a total score of 44. The scale is graded 0-4. A low score indicates a good effect. This change in FACT-NTX scale score indicates the proportion of patients with successful outcomes.
Time frame: Baseline, 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cryotherapy | Proportion of Patients With Successful Outcomes (<5-point Decrease in FACT-NTX From Baseline) | 0.45 Proportion of Patients |
| Compression Therapy | Proportion of Patients With Successful Outcomes (<5-point Decrease in FACT-NTX From Baseline) | 0.59 Proportion of Patients |
| Control Arm (Loose Glove/Sock) | Proportion of Patients With Successful Outcomes (<5-point Decrease in FACT-NTX From Baseline) | 0.52 Proportion of Patients |
Secondary
Adherence to Study Intervention
The number of participants who adhered to the intervention. Adherence is defined as wearing the assigned gloves and socks for greater than or equal to 80% of infusions.
Time frame: Up to 24 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cryotherapy | Adherence to Study Intervention | 80% or Above | 7 Participants |
| Cryotherapy | Adherence to Study Intervention | Below 80% | 13 Participants |
| Compression Therapy | Adherence to Study Intervention | 80% or Above | 16 Participants |
| Compression Therapy | Adherence to Study Intervention | Below 80% | 6 Participants |
| Control Arm (Loose Glove/Sock) | Adherence to Study Intervention | Below 80% | 5 Participants |
| Control Arm (Loose Glove/Sock) | Adherence to Study Intervention | 80% or Above | 16 Participants |
Secondary
Average Time to Complete 'Timed Get up and go' Test
The 'timed get up and go' test is a rapid and widely used clinical performance-based measure of lower extremity function, mobility, and fall risk. Subjects are asked to stand up from a standard chair (seat height between 44 and 47 cm), walk a distance of 3 m (marked on the floor) at a comfortable pace, turn, walk back and sit down. Time will be measured in seconds. Shorter times indicate better performance.
Time frame: Up to 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cryotherapy | Average Time to Complete 'Timed Get up and go' Test | Week 12 | 15.48 Seconds | Standard Deviation 7.98 |
| Cryotherapy | Average Time to Complete 'Timed Get up and go' Test | Week 24 | 17.45 Seconds | Standard Deviation 8.03 |
| Compression Therapy | Average Time to Complete 'Timed Get up and go' Test | Week 12 | 12.36 Seconds | Standard Deviation 3.75 |
| Compression Therapy | Average Time to Complete 'Timed Get up and go' Test | Week 24 | 13.93 Seconds | Standard Deviation 3.04 |
| Control Arm (Loose Glove/Sock) | Average Time to Complete 'Timed Get up and go' Test | Week 12 | 15.18 Seconds | Standard Deviation 4.54 |
| Control Arm (Loose Glove/Sock) | Average Time to Complete 'Timed Get up and go' Test | Week 24 | 14.84 Seconds | Standard Deviation 5.5 |
Secondary
Change in Nail Toxicity
The number of participants with a change in cutaneous toxicity and onycholysis will be assessed by a healthcare professional using the National Cancer Institute Common Toxicity Criteria (Version 2), specifically nail changes. Grade 1 includes discoloration, ridging (koilonychia), or pitting of the nails and Grade 2 is partial or complete loss of nail(s) or pain in the nail beds. A higher grade indicates more nail toxicity.
Time frame: Baseline, 12 weeks, 24 weeks
Population: The numbers analyzed at the each of the respective timepoints are the number of participants from which the data was collected.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cryotherapy | Change in Nail Toxicity | Week 12 | Staged decreased | 0 Participants |
| Cryotherapy | Change in Nail Toxicity | Week 12 | Stage increased | 10 Participants |
| Cryotherapy | Change in Nail Toxicity | Week 12 | Stage stayed the same | 4 Participants |
| Cryotherapy | Change in Nail Toxicity | Week 24 | Staged decreased | 0 Participants |
| Cryotherapy | Change in Nail Toxicity | Week 24 | Stage increased | 7 Participants |
| Cryotherapy | Change in Nail Toxicity | Week 24 | Stage stayed the same | 1 Participants |
| Compression Therapy | Change in Nail Toxicity | Week 24 | Stage stayed the same | 6 Participants |
| Compression Therapy | Change in Nail Toxicity | Week 12 | Staged decreased | 0 Participants |
| Compression Therapy | Change in Nail Toxicity | Week 24 | Staged decreased | 0 Participants |
| Compression Therapy | Change in Nail Toxicity | Week 24 | Stage increased | 7 Participants |
| Compression Therapy | Change in Nail Toxicity | Week 12 | Stage increased | 7 Participants |
| Compression Therapy | Change in Nail Toxicity | Week 12 | Stage stayed the same | 8 Participants |
| Control Arm (Loose Glove/Sock) | Change in Nail Toxicity | Week 12 | Stage increased | 10 Participants |
| Control Arm (Loose Glove/Sock) | Change in Nail Toxicity | Week 12 | Stage stayed the same | 5 Participants |
| Control Arm (Loose Glove/Sock) | Change in Nail Toxicity | Week 24 | Stage stayed the same | 3 Participants |
| Control Arm (Loose Glove/Sock) | Change in Nail Toxicity | Week 24 | Staged decreased | 1 Participants |
| Control Arm (Loose Glove/Sock) | Change in Nail Toxicity | Week 12 | Staged decreased | 1 Participants |
| Control Arm (Loose Glove/Sock) | Change in Nail Toxicity | Week 24 | Stage increased | 11 Participants |
Secondary
Change in NCI-CTCAE Grade for CIPN
National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) is a subjective method to evaluate CIPN which is performed by a healthcare professional. The patient's peripheral sensory neuropathy, peripheral motor neuropathy, dysesthesia, paresthesia and neuralgia will be graded on a scale of 1 to 5 depending on severity with 1 indicating a better outcome.
Time frame: Baseline, 12, and 24 weeks
Population: The numbers analyzed at the each of the respective timepoints are the number of participants from which the data was collected.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cryotherapy | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage stayed the same | 6 Participants |
| Cryotherapy | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage decreased | 1 Participants |
| Cryotherapy | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage stayed the same | 5 Participants |
| Cryotherapy | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage increased | 11 Participants |
| Cryotherapy | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage increased | 10 Participants |
| Cryotherapy | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage decreased | 1 Participants |
| Compression Therapy | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage increased | 8 Participants |
| Compression Therapy | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage increased | 8 Participants |
| Compression Therapy | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage stayed the same | 12 Participants |
| Compression Therapy | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage decreased | 0 Participants |
| Compression Therapy | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage stayed the same | 13 Participants |
| Compression Therapy | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage decreased | 0 Participants |
| Control Arm (Loose Glove/Sock) | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage stayed the same | 10 Participants |
| Control Arm (Loose Glove/Sock) | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage decreased | 1 Participants |
| Control Arm (Loose Glove/Sock) | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage increased | 7 Participants |
| Control Arm (Loose Glove/Sock) | Change in NCI-CTCAE Grade for CIPN | Week 12 | Stage stayed the same | 10 Participants |
| Control Arm (Loose Glove/Sock) | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage increased | 7 Participants |
| Control Arm (Loose Glove/Sock) | Change in NCI-CTCAE Grade for CIPN | Week 24 | Stage decreased | 2 Participants |
Secondary
Comfort With Intervention Scale Score
Comfort with the study intervention will be assessed on a 4-point scale, (0=dissatisfied; 1=not satisfied; 2=satisfied; 3=very satisfied) with 3 indicating a better outcome.
Time frame: Up to 24 weeks
Population: The numbers analyzed at the each of the respective timepoints are the number of participants from which the data was collected.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cryotherapy | Comfort With Intervention Scale Score | Week 24 | Not Satisfied | 2 Participants |
| Cryotherapy | Comfort With Intervention Scale Score | Week 12 | Not Satisfied | 0 Participants |
| Cryotherapy | Comfort With Intervention Scale Score | Week 24 | Satisfied | 5 Participants |
| Cryotherapy | Comfort With Intervention Scale Score | Week 24 | Very Satisfied | 2 Participants |
| Cryotherapy | Comfort With Intervention Scale Score | Week 12 | Dissatisfied | 4 Participants |
| Cryotherapy | Comfort With Intervention Scale Score | Week 12 | Very Satisfied | 3 Participants |
| Cryotherapy | Comfort With Intervention Scale Score | Week 24 | Dissatisfied | 3 Participants |
| Cryotherapy | Comfort With Intervention Scale Score | Week 12 | Satisfied | 9 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 24 | Not Satisfied | 0 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 24 | Dissatisfied | 1 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 12 | Very Satisfied | 6 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 24 | Satisfied | 10 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 12 | Not Satisfied | 0 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 12 | Dissatisfied | 2 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 24 | Very Satisfied | 7 Participants |
| Compression Therapy | Comfort With Intervention Scale Score | Week 12 | Satisfied | 13 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 24 | Very Satisfied | 3 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 12 | Dissatisfied | 0 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 12 | Satisfied | 12 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 12 | Very Satisfied | 3 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 24 | Dissatisfied | 0 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 24 | Not Satisfied | 1 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 24 | Satisfied | 11 Participants |
| Control Arm (Loose Glove/Sock) | Comfort With Intervention Scale Score | Week 12 | Not Satisfied | 1 Participants |
Secondary
Subjects Perceived Pain and Pressure Using Neuropen Test
Evaluation of other sensory endpoints including touch, pressure and pain will be evaluated using a Neuropen. Touch and pressure sensation will be assessed using a 10-g monofilament on the subject's dominant foot. Pain and subjective sharpness sensation will be assessed using the Neuropen on the dominant foot. The spring mechanism is calibrated to exert a force of 40 grams to help identify subjects with loss of pain sensation. Ten points on the foot are tested. If the participant detects pain and pressure on less than 8 points, pain and pressure perception are considered diminished. Perception on 8 points of the foot or greater is considered a better outcome.
Time frame: Up to 24 weeks
Population: The numbers analyzed at the each of the respective timepoints are the number of participants from which the data was collected.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Touch and Pressure | <8 points of the foot | 3 Participants |
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Touch and Pressure | >=8 points of the foot | 11 Participants |
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Pain | <8 points of the foot | 0 Participants |
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Pain | >=8 points of the foot | 14 Participants |
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Touch and Pressure | <8 points of the foot | 3 Participants |
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Touch and Pressure | >=8 points of the foot | 10 Participants |
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Pain | <8 points of the foot | 1 Participants |
| Cryotherapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Pain | >=8 points of the foot | 12 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Pain | <8 points of the foot | 1 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Pain | <8 points of the foot | 0 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Pain | >=8 points of the foot | 17 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Touch and Pressure | <8 points of the foot | 0 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Touch and Pressure | >=8 points of the foot | 17 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Touch and Pressure | <8 points of the foot | 0 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Touch and Pressure | >=8 points of the foot | 18 Participants |
| Compression Therapy | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Pain | >=8 points of the foot | 17 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Pain | <8 points of the foot | 0 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Touch and Pressure | >=8 points of the foot | 13 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Touch and Pressure | <8 points of the foot | 0 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 12: Pain | >=8 points of the foot | 13 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Pain | <8 points of the foot | 0 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Touch and Pressure | >=8 points of the foot | 17 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Touch and Pressure | <8 points of the foot | 0 Participants |
| Control Arm (Loose Glove/Sock) | Subjects Perceived Pain and Pressure Using Neuropen Test | Week 24: Pain | >=8 points of the foot | 17 Participants |
Secondary
Tandem and Unipedal Stance Test
Balance will be assessed using the tandem and unipedal stance test. In this assessment, the subject stands with one foot in front of the other (heel to toe) (30 seconds), then on one leg with: eyes open (60 seconds), eyes closed (30 seconds), and eyes open with head rotation (30 seconds) with arms held comfortably at the side. The test was accepted failure when the stance foot shifted in any way or the nonstance foot touched the ground. Tests are recorded as achieved (yes) or not achieved (no).
Time frame: Up to 24 weeks
Population: The numbers analyzed at the each of the respective timepoints and assessments are the number of participants from which the data was collected.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cryotherapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open | No | 6 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open | Yes | 7 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes closed | No | 13 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes closed | Yes | 0 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open, rotated | No | 11 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open, rotated | Yes | 1 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open | No | 10 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open | Yes | 3 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes closed | No | 13 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes closed | Yes | 0 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open, rotated | No | 12 Participants |
| Cryotherapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open, rotated | Yes | 1 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open, rotated | Yes | 2 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open | No | 12 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open | No | 11 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes closed | No | 16 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open | Yes | 7 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open, rotated | Yes | 4 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open, rotated | No | 14 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes closed | No | 17 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open | Yes | 5 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open, rotated | No | 15 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 12: One leg, eyes closed | Yes | 2 Participants |
| Compression Therapy | Tandem and Unipedal Stance Test | Week 24: One leg, eyes closed | Yes | 0 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 12: One leg, eyes closed | Yes | 0 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open, rotated | No | 14 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 24: One leg, eyes closed | Yes | 3 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open, rotated | Yes | 1 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open | No | 11 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open | Yes | 6 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open, rotated | No | 14 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open | No | 11 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 12: One leg, eyes open | Yes | 4 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 24: One leg, eyes closed | No | 14 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 12: One leg, eyes closed | No | 15 Participants |
| Control Arm (Loose Glove/Sock) | Tandem and Unipedal Stance Test | Week 24: One leg, eyes open, rotated | Yes | 3 Participants |
Secondary
Vibration Perception and Disappearance Threshold
Study participants will be assessed for development of sensory neurological dysfunction. Vibration perception will be assessed using a tuning fork. Vibration threshold will be tested on the bilateral dorsum of the distal interphalangeal joint of the index finger and dorsum of the interphalangeal joint of the hallux. Subjects will be asked to indicate when the vibration stimulus is initially felt (perception threshold) and when the stimulus disappears (disappearance threshold.) The vibration perception threshold is the average of three paired measurements.
Time frame: Up to 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 12: Hand Perception | 10.95 Seconds | Standard Deviation 7.34 |
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 12: Foot Perception | 20.55 Seconds | Standard Deviation 13.13 |
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 24: Hand Perception | 9.79 Seconds | Standard Deviation 6.28 |
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 24: Foot Perception | 24.38 Seconds | Standard Deviation 18.54 |
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 12: Hand Disapperance | 4.43 Seconds | Standard Deviation 3.87 |
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 12: Foot Disappearance | 12.12 Seconds | Standard Deviation 9.53 |
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 24: Hand Disappearance | 3.33 Seconds | Standard Deviation 3.39 |
| Cryotherapy | Vibration Perception and Disappearance Threshold | Week 24: Foot Disappearance | 10.52 Seconds | Standard Deviation 6.15 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 24: Hand Perception | 7.82 Seconds | Standard Deviation 3.61 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 24: Hand Disappearance | 3.04 Seconds | Standard Deviation 2.57 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 24: Foot Perception | 20.84 Seconds | Standard Deviation 13.42 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 12: Hand Disapperance | 3.09 Seconds | Standard Deviation 1.96 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 12: Foot Disappearance | 11.33 Seconds | Standard Deviation 8.51 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 12: Hand Perception | 7.70 Seconds | Standard Deviation 3.02 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 12: Foot Perception | 17.16 Seconds | Standard Deviation 12.25 |
| Compression Therapy | Vibration Perception and Disappearance Threshold | Week 24: Foot Disappearance | 12.90 Seconds | Standard Deviation 10.36 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 24: Hand Perception | 7.61 Seconds | Standard Deviation 2.3 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 12: Foot Perception | 13.29 Seconds | Standard Deviation 6.29 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 12: Hand Perception | 8.47 Seconds | Standard Deviation 4.72 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 24: Foot Perception | 13.84 Seconds | Standard Deviation 5.56 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 24: Hand Disappearance | 2.98 Seconds | Standard Deviation 2.23 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 12: Foot Disappearance | 7.53 Seconds | Standard Deviation 5.54 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 12: Hand Disapperance | 3.60 Seconds | Standard Deviation 4.02 |
| Control Arm (Loose Glove/Sock) | Vibration Perception and Disappearance Threshold | Week 24: Foot Disappearance | 6.08 Seconds | Standard Deviation 3.91 |