Post-Mastectomy Chronic Pain Syndrome
Conditions
Keywords
neuroma,outcome-assessment health care, post-mastectomy, outcome-assessment health care, post-mastectomy, neuroma
Brief summary
Post-mastectomy pain due to nerve injury leads to long-term opioid use and diminished quality-of-life. The investigators on this study will evaluate the regenerative peripheral nerve interface (RPNI), a novel surgical approach to neuroma treatment, to improve patient-reported post-mastectomy pain and definitively treat intercostal neuromas after mastectomy.
Detailed description
Up to 40% of patients who undergo mastectomy suffer from chronic pain, defined as pain lasting greater than three months. Chronic post-mastectomy pain due to nerve injury leads to long-term opioid use and diminished quality-of-life. A novel surgical approach to neuroma treatment, the regenerative peripheral nerve interface (RPNI) developed to treat painful neuromas associated with limb amputation has shown significant reductions in patient-reported pain. RPNI surgery is now available through Michigan Medicine's Multi-Disciplinary Peripheral Nerve (MDPN) Clinic to improve post-mastectomy pain and definitively treat intercostal neuromas following mastectomy. Using patient-reported outcomes and clinical data the investigators will evaluate the use of RPNI surgery to reduce persistent post- mastectomy pain in women seeking surgical consultation through the Plastic Surgery or MDPN clinics.
Interventions
The regenerative peripheral nerve interface (RPNI) has emerged as a novel strategy to treat neuromas in peripheral nerves. The RPNI consists of the residual peripheral nerve end implanted in a skeletal muscle graft, following surgical resection of the injured terminal nerve portion (neuroma). The free muscle graft is separated from its native nerve innervation, leaving open neuromuscular junctions for ingrowth and attachment of nerve fibers from the implanted nerve.
Sponsors
National Cancer Institute (NCI)
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria: * Reporting post-mastectomy pain at least six months removed from mastectomy or partial mastectomy (lumpectomy). * Willing to comply with all study procedures and be available for the duration of the study * Fluent in English * Women of reproductive potential must use highly effective contraception (specify methods of contraception acceptable for the study, e.g., licensed hormonal methods) and/or willingness to undergo a pregnancy test.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study: * Previous surgical management for chronic post-mastectomy pain * Signs/symptoms which are not suggestive of neuropathic pain based on physical exam at time of consultation. * Pregnancy or lactation * Men will not be enrolled in this study due to the low prevalence of male mastectomy. * Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Level | baseline, and 9 months post surgery | The use of RPNI surgery to reduce post-mastectomy pain will be evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. Numerical Pain Rating Scale (0-10)- 10 indicating more pain Short Form McGill Pain Questionnaire 2 (0-10)- 10 indicating more pain Pain Catastrophizing Score (0-52)- 52 indicating more pain PROMIS Intensity (0-12)- 12 indicating more pain PROMIS Interference (0-24)- 24 indicating more pain PROMIS Neuropathic (0-20)- 20 indicating more pain |
| Change in Depression/Anxiety Scores | baseline, and 9 months post surgery | Evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. Patient Health Questionnaire-9 range is 0-27. 27 indicates a worse outcome. Generalized Anxiety Disorder-7 range is 0-21. 21 indicates a worse outcome. |
| Change in Opioid Consumption (Number of Opioid Medications) | baseline, and 9 months post surgery | Evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. |
| Freedom From Neuroma Recurrence Evaluated by Physical Exam | 24 months post enrollment | Data will be derived from standard clinical care for patients seeking surgical management of post-mastectomy chronic pain. Physical examinations will be performed at the time of patient enrollment and subsequent follow-up visits, as part of routine clinical evaluation, up to approximately 9 months after RPNI surgery. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. |
| Freedom From Neuroma Recurrence Evaluated by Ultrasound | 24 months post enrollment | Data will be derived from standard clinical care for patients seeking surgical management of post-mastectomy chronic pain. Ultrasound will be performed at the time of patient enrollment and subsequent follow-up visits, as part of routine clinical evaluation, up to approximately 9 months after RPNI surgery. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. |
| Change in Opioid Consumption (Oral Morphine Equivalents) | baseline, and 9 months post surgery | Evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) Using evaluative ultrasound measurements and a standard panel of patient-reported outcome measures (PROMs) to measure pain experience, anxiety and depression, patients will be evaluated at baseline (T1=0months), pre-operatively following 3 months of standard neuropathic pain management therapy (T2=3months) and at three months (T3=6months) and nine months (T4=12months) post RPNI surgery.
Regenerative Peripheral Nerve Interface: The regenerative peripheral nerve interface (RPNI) has emerged as a novel strategy to treat neuromas in peripheral nerves. The RPNI consists of the residual peripheral nerve end implanted in a skeletal muscle graft, following surgical resection of the injured terminal nerve portion (neuroma). The free muscle graft is separated from its native nerve innervation, leaving open neuromuscular junctions for ingrowth and attachment of nerve fibers from the implanted nerve. | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Regenerative Peripheral Nerve Interface (RPNI) |
|---|---|
| Age, Customized 20-29 years | 1 Participants |
| Age, Customized 30-39 years | 1 Participants |
| Age, Customized 40-49 years | 9 Participants |
| Age, Customized 50-59 years | 5 Participants |
| Age, Customized 60-69 years | 8 Participants |
| Age, Customized 70-79 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Change in Depression/Anxiety Scores
Evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. Patient Health Questionnaire-9 range is 0-27. 27 indicates a worse outcome. Generalized Anxiety Disorder-7 range is 0-21. 21 indicates a worse outcome.
Time frame: baseline, and 9 months post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Depression/Anxiety Scores | Patient Health Questionnaire-9- Preoperative | 10.3 score on a scale | Standard Error 1.3 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Depression/Anxiety Scores | Patient Health Questionnaire-9- Postoperative | 7.2 score on a scale | Standard Error 1.4 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Depression/Anxiety Scores | Generalized Anxiety Disorder-7- Preoperative | 7.3 score on a scale | Standard Error 1.1 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Depression/Anxiety Scores | Generalized Anxiety Disorder-7- postoperative | 4.3 score on a scale | Standard Error 1.2 |
Primary
Change in Opioid Consumption (Number of Opioid Medications)
Evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops.
Time frame: baseline, and 9 months post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Opioid Consumption (Number of Opioid Medications) | Number of Opioid Medications- Preoperative | 1.3 Opioid medications | Standard Error 0.2 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Opioid Consumption (Number of Opioid Medications) | Number of Opioid Medications- Postoperative | 0.4 Opioid medications | Standard Error 0.2 |
Primary
Change in Opioid Consumption (Oral Morphine Equivalents)
Evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops.
Time frame: baseline, and 9 months post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Opioid Consumption (Oral Morphine Equivalents) | Oral Morphine Equivalents (mg)- Preoperative | 43.3 mg morphine equivalent | Standard Error 11.4 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Opioid Consumption (Oral Morphine Equivalents) | Oral Morphine Equivalents (mg)- Postoperative | 12.0 mg morphine equivalent | Standard Error 4.9 |
Primary
Change in Pain Level
The use of RPNI surgery to reduce post-mastectomy pain will be evaluated by validated patient-reported outcome (PRO) surveys administered at 4 timepoints: at baseline (at time of enrollment), at the RPNI pre-operative visit (approximately 3 months after enrollment), and at approximately 3 and 9 months after RPNI surgery. The average time of study involvement for each patient will be 12 months. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops. Numerical Pain Rating Scale (0-10)- 10 indicating more pain Short Form McGill Pain Questionnaire 2 (0-10)- 10 indicating more pain Pain Catastrophizing Score (0-52)- 52 indicating more pain PROMIS Intensity (0-12)- 12 indicating more pain PROMIS Interference (0-24)- 24 indicating more pain PROMIS Neuropathic (0-20)- 20 indicating more pain
Time frame: baseline, and 9 months post surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | Numerical Pain Rating Scale- Preoperative Score | 6.9 score on a scale | Standard Error 0.4 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | Numerical Pain Rating Scale- Postoperative Score | 0.6 score on a scale | Standard Error 0.3 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | Short Form McGill Pain Questionnaire 2- Preoperative | 4.4 score on a scale | Standard Error 0.5 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | Short Form McGill Pain Questionnaire 2- Postoperative | 2.5 score on a scale | Standard Error 0.6 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | Pain Catastrophizing Score- Preoperative | 27.5 score on a scale | Standard Error 3 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | Pain Catastrophizing Score- Postoperative | 14.1 score on a scale | Standard Error 2.9 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | PROMIS Intensity- Preoperative | 7.9 score on a scale | Standard Error 0.5 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | PROMIS Intensity- Postoperative | 4.9 score on a scale | Standard Error 0.8 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | PROMIS Interference- Preoperative | 16.2 score on a scale | Standard Error 1.3 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | PROMIS Interference- Post Operative | 11.0 score on a scale | Standard Error 2 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | PROMIS Neuropathic- Preoperative | 8.6 score on a scale | Standard Error 1.4 |
| Regenerative Peripheral Nerve Interface (RPNI) | Change in Pain Level | PROMIS Neuropathic- Postoperative | 6.0 score on a scale | Standard Error 1.4 |
Primary
Freedom From Neuroma Recurrence Evaluated by Physical Exam
Data will be derived from standard clinical care for patients seeking surgical management of post-mastectomy chronic pain. Physical examinations will be performed at the time of patient enrollment and subsequent follow-up visits, as part of routine clinical evaluation, up to approximately 9 months after RPNI surgery. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops.
Time frame: 24 months post enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) | Freedom From Neuroma Recurrence Evaluated by Physical Exam | 20 Participants |
Primary
Freedom From Neuroma Recurrence Evaluated by Ultrasound
Data will be derived from standard clinical care for patients seeking surgical management of post-mastectomy chronic pain. Ultrasound will be performed at the time of patient enrollment and subsequent follow-up visits, as part of routine clinical evaluation, up to approximately 9 months after RPNI surgery. Patients enrolled during the first year of the study's 2-year recruitment period may be followed until the study stops.
Time frame: 24 months post enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Regenerative Peripheral Nerve Interface (RPNI) | Freedom From Neuroma Recurrence Evaluated by Ultrasound | 20 Participants |