Shoulder Pain, Stroke
Conditions
Keywords
Stroke, Shoulder Pain, Electrical stimulation, Neuromuscular stimulation, Intramuscular stimulation, Physical Therapy
Brief summary
Hemiplegic shoulder pain (HSP) affects up to 60% of moderate to severely impaired stroke survivors. HSP is associated with poor rehabilitation outcomes, including interference with activities of daily living (ADLs) and poor quality of life (QoL). While many treatments for HSP have been proposed, most do not result in long-term relief of pain. The investigators developed the use of intramuscular peripheral nerve stimulation (PNS) for the treatment of HSP, which involves the temporary placement of a percutaneous intramuscular electrode to stimulate the axillary nerve motor points to the deltoid muscle. A systematic review of randomized controlled trials (RCT) concluded that intramuscular PNS was the only treatment to provide long-term relief of pain for those with HSP. However, physical therapy (PT), which focuses on correcting biomechanics, is the most commonly prescribed treatment for HSP and is recommended by multiple practice guidelines. Prior to acceptance by the clinical community, the superiority of PNS to a course of PT must be demonstrated. The investigators completed a pilot RCT comparing PNS to PT and 67% vs. 25% of participants experienced successful pain relief (i.e., ≥ 2-pt or 30% reduction) from PNS and PT, respectively. Thus, the primary objective of this 2-site RCT is to confirm the findings of this preliminary pilot RCT. Combining PNS and PT, which may be how PNS is actually implemented in clinical practice, may have a synergistic therapeutic effect. Thus, the second objective of this RCT is to determine if multimodal treatment of HSP with PNS + PT is more efficacious for pain relief than PNS alone or PT alone. Mechanisms also will be explored.
Detailed description
Study Summary: This is a multi-site, placebo controlled, double-blinded RCT to confirm the superiority of PNS over PT in reducing HSP, and to determine if multimodal treatment of HSP with PNS + PT is more efficacious than PNS or PT alone. The standard of care for treating shoulder pain is to try several options, most commonly including medications, injections and therapy. Candidates considering this study likely have tried some treatments but without lasting success. Ninety-six participants will be randomized to receive PNS + PT, PNS + sham-PT, or sham-PNS + PT. The PNS + PT group will receive active PNS therapy for 6 hours per day for 3 weeks along with 8 sessions of PT to improve biomechanics of the affected shoulder. The PNS+ sham-PT group will receive active PNS therapy and sham-PT, consisting of placebo ultrasound, application of inert gel, lower limb strengthening, and walking exercises. The sham-PNS + PT group will receive a percutaneous lead in a similar manner as the active therapy groups, but with sham-stimulation, along with 8 sessions of PT. Measures of pain, pain interference with ADLs, QoL, shoulder biomechanics (shoulder abduction torque, shoulder kinematics, and Fugl-Meyer score), and measures of central sensitization (pain thresholds, secondary hyperalgesia, and temporal summation) will be assessed at baseline and at weeks 4 (end of treatment), 8, 12, 16, 20, 24, and 28.
Interventions
DEVICEPeripheral Nerve Stimulation
The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad has an embedded power source but also serves as the anode. The 1-channel stimulator outputs a biphasic current waveform with current pulse parameter ranges suitable for PNS. The percutaneous lead is inserted using an introducer (like a hypodermic needle) which is withdrawn and the lead is retained in the muscle by a barb at its tip. After a 1-week stabilization period, stimulation is initiated (6 hrs/day). The duty cycle and daily dose remain constant, but stimulus parameters may be adjusted by the research staff as deemed appropriate. The treatment period is 3 weeks after which the lead will be removed. Total time of electrode implantation is no more than 29 days.
OTHERPhysical Therapy
Participants will receive 8 60-minute sessions of outpatient therapy over a 4 week period concurrent with PNS or sham-PNS treatment. Therapy may include: Proper Positioning and Handling, Therapeutic positioning and Strengthening Exercises, Mirror Therapy, Task-specific Therapy, Home Exercise Program, and a Mental Practice program.
OTHERSham-PT
Participants randomized to sham-PT will receive 8 60-minute sessions with therapists with the goal of controlling for the effect of regular contact with a therapist and study staff in a therapeutic environment. Participants will undergo a hands-on evaluation and re-evaluation before and after treatment. Therapists will provide sham ultrasound therapy and light application of inert gel to the shoulder for 10 minutes, Pre-Gait Training or Gait training, Exercise therapy, and relaxation therapy.
DEVICESham-PNS
The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad has an embedded power source.The stimulator will appear to function as normal though will not deliver electrical current to the electrode. The subjects will be prescribed 6 hours of sham-stimulation per day for 3 weeks.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Case Western Reserve University
Shirley Ryan AbilityLab
MetroHealth Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* shoulder pain localized to the glenohumeral joint, subacromial area or deltoid insertion associated with: a) rest; b) passive abduction or external rotation range of motion (ROM); c) active abduction ROM; or, d) manual palpation; * shoulder pain onset or worsening after the most recent stroke; * weakness of shoulder abductors (≤4/5 on Medical Research Council (MRC) scale if isolated movement is present); * ≥ 21-yrs old; \< 90-yrs old; * time of stroke ≥ 3-mo; * duration of HSP ≥3-mo; * HSP with moderate to severe pain (BPI SF-3 ≥ 4); * cognitive and communication ability to fulfill study requirements (cognitive ability based upon a score of ≥24 on the Mini Mental Status Exam (MMSE)); * availability of reliable adult who can assist with study procedures if necessary; * willing and able to report shoulder pain and other conditions and complete study visits throughout the 4 month study period.
Exclusion criteria
* joint or overlying skin infection or history of recurrent skin infections; * insensate skin; * need to take \> 1 opioid and \> 1 nonopioid analgesic medication for HSP; * regular intake of pain medications for another chronic pain; * botox injection or subacromial steroid injections to the shoulder within the past 12 weeks; * receiving occupational therapy (OT) or PT for HSP; * bleeding disorder or international normalized ratio (INR) \> 3.0; * sensitivity to skin surface electrodes and/or medical-grade adhesives, gels, tapes; * medical instability; * pregnancy; * uncontrolled seizures (\>1/mo for 6-mo); * history of cardiac arrhythmia with hemodynamic instability; * history of lidocaine allergy; * history of Parkinson's disease, spinal cord injury (SCI), traumatic brain injury (TBI), multiple sclerosis (MS), or ipsilateral upper extremity (UE) lower motor neuron lesion; * history of complex regional pain syndrome, myofacial pain syndrome, other pain conditions (investigator discretion); * cardiac pacemaker or other implanted electronic device; * history of valvular heart disease (artificial valves, requiring antibiotics for procedures, etc.); * severely impaired communication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | Baseline, 4 weeks(end of treatment), 16 weeks, 28 weeks | Brief Pain Inventory Short Form 3: The BPI has excellent psychometrics and is recommended for the assessment of pain in clinical trials. The developers of the BPI recommend BPI SF-3, the pain worst rating, as the primary response metric. The question asks participants to rate their worst pain in the prior 7-d on a 0 to 10 numeric rating scale, where 0 indicates No pain and 10 indicates Pain as bad as you can imagine. Lower score means better outcome Baseline is absolute value and change value is reported for 4 weeks, 16 weeks and 28 weeks. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (Number of Participants With Related Adverse Events) | Week 2 - Week 5 | Related adverse events are documented as Safety data. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PNS + PT The PNS+PT Group will receive peripheral nerve stimulation treatment for three weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a 1 week electrode stabilization period,and also receive eight 60-minute sessions of outpatient physical therapy focused on shoulder pain over the same 4 week period. Peripheral Nerve Stimulation: The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad serves as the anode. The 1-channel stimulator outputs a biphasic current waveform with current pulse parameter ranges suitable for PNS. The percutaneous lead is inserted using an introducer (like a hypodermic needle) which is withdrawn and the lead is retained in the muscle by a barb at its tip. After a 1-week stabilization period, stimulation is initiated (6 hrs/day). The duty cycle and daily dose remain constant, but stimulus parameters may be adjusted by the research staff as deemed appropriate. The treatment period is 3 weeks after which the lead will be removed. Total time of electrode implantation is no more than 29 days. Physical Therapy: Participants will receive 8 60-minute sessions of outpatient therapy over a 4 week period concurrent with PNS or sham-PNS treatment. Therapy may include: Proper Position and Handling, Therapeutic positioning and Strengthening Exercises, Mirror Therapy, Task-specific Therapy, Home Exercise Program, and a Mental Practice program. | 31 |
| PNS + Sham-PT The PNS + sham-PT Group will receive peripheral nerve stimulation treatment for 3weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a 1week electrode stabilization period, and also receive eight 60-minute sessions of sham outpatient physical therapy not focused on shoulder pain over the same four week period. Peripheral Nerve Stimulation: The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad serves as the anode. The 1-channel stimulator outputs a biphasic current waveform with current pulse parameter ranges suitable for PNS. The percutaneous lead is inserted using an introducer (like a hypodermic needle) which is withdrawn and the lead is retained in the muscle by a barb at its tip. After a 1-week stimulation is initiated (6 hrs/day). The duty cycle and daily dose remain constant, but stimulus parameters may be adjusted by the research staff as appropriate. The treatment period is 3 weeks after which the lead is removed. Total time of electrode implantation is no more than 29 days. Sham-PT: Participants randomized to sham-PT will receive 8 60-minute sessions with therapists with the goal of controlling for the effect of regular contact with a therapist in a therapeutic environment. Therapists will provide sham ultrasound therapy and light application of inert gel to the shoulder for 10 minutes, Pre-Gait Training or Gait training, Exercise therapy, and relaxation therapy. | 32 |
| Sham-PNS + PT The sham-PNS + PT Group will receive sham peripheral nerve stimulation treatment (which will not produce muscle contraction) for three weeks (6 hours daily) with an Intramuscular Electrical Stimulator following a one week electrode stabilization period, and also receive eight 60-minute sessions of outpatient physical therapy focused on shoulder pain over the same four week period.
Physical Therapy: Participants will receive 8 60-minute sessions of outpatient therapy over a 4 week period concurrent with PNS or sham-PNS treatment. Therapy may include: Proper Positioning and Handling, Therapeutic positioning and Strengthening Exercises, Mirror Therapy, Task-specific Therapy, Home Exercise Program, and a Mental Practice program.
Sham-PNS: The stimulation system includes an external stimulator, percutaneous lead and pad. The stimulator snaps onto the pad. The pad has an embedded power source.The stimulator will appear to function as normal though will not deliver electrical current to the electrode. The subjects will be prescribed 6 hours of sham-stimulation per day for 3 weeks. | 33 |
| Total | 96 |
Baseline characteristics
| Characteristic | Total | PNS + PT | PNS + Sham-PT | Sham-PNS + PT |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 2 Participants | 8 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 76 Participants | 29 Participants | 24 Participants | 23 Participants |
| Age, Continuous | 58.2 years STANDARD_DEVIATION 9.35 | 56.2 years STANDARD_DEVIATION 8.4 | 59.5 years STANDARD_DEVIATION 9.6 | 58.9 years STANDARD_DEVIATION 9.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 43 Participants | 17 Participants | 11 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 47 Participants | 13 Participants | 20 Participants | 14 Participants |
| Region of Enrollment United States | 96 participants | 31 participants | 32 participants | 33 participants |
| Sex: Female, Male Female | 36 Participants | 10 Participants | 13 Participants | 13 Participants |
| Sex: Female, Male Male | 60 Participants | 21 Participants | 19 Participants | 20 Participants |
| Short Form (SF) Question 3 (BPI-SF3) absolute value | 7.542 units on a scale | 7.129 units on a scale | 7.406 units on a scale | 8.061 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 31 | 0 / 32 | 1 / 33 |
| other Total, other adverse events | 19 / 31 | 21 / 32 | 16 / 33 |
| serious Total, serious adverse events | 2 / 31 | 3 / 32 | 5 / 33 |
Outcome results
Primary
Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline
Brief Pain Inventory Short Form 3: The BPI has excellent psychometrics and is recommended for the assessment of pain in clinical trials. The developers of the BPI recommend BPI SF-3, the pain worst rating, as the primary response metric. The question asks participants to rate their worst pain in the prior 7-d on a 0 to 10 numeric rating scale, where 0 indicates No pain and 10 indicates Pain as bad as you can imagine. Lower score means better outcome Baseline is absolute value and change value is reported for 4 weeks, 16 weeks and 28 weeks.
Time frame: Baseline, 4 weeks(end of treatment), 16 weeks, 28 weeks
Population: Some participants drop out, withdraw consent, or are lost before later visits or assessments.~Their later data points are missing, so they're not included in analyses for those timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | Baseline (absolute Value) | 7.1 units on a scale |
| PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | End of Treatment (change value) | -2.8 units on a scale |
| PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | 16 weeks (change value) | -3.9 units on a scale |
| PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | 28 weeks (change value) | -2.8 units on a scale |
| PNS + sham-PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | 28 weeks (change value) | -2.1 units on a scale |
| PNS + sham-PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | Baseline (absolute Value) | 7.4 units on a scale |
| PNS + sham-PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | 16 weeks (change value) | -2.4 units on a scale |
| PNS + sham-PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | End of Treatment (change value) | -2.4 units on a scale |
| sham-PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | 28 weeks (change value) | -3.1 units on a scale |
| sham-PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | End of Treatment (change value) | -2.4 units on a scale |
| sham-PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | 16 weeks (change value) | -2.9 units on a scale |
| sham-PNS + PT | Brief Pain Inventory (BPI)- Short Form (SF) Question 3 (BPI-SF3) - Mean Change From Baseline | Baseline (absolute Value) | 8.1 units on a scale |
Other Pre-specified
Adverse Events (Number of Participants With Related Adverse Events)
Related adverse events are documented as Safety data.
Time frame: Week 2 - Week 5
Population: All subject who completed Baseline, Treatment and End of treatment assessments are included in the related adverse events reporting
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PNS + PT | Adverse Events (Number of Participants With Related Adverse Events) | 13 Participants |
| PNS + sham-PT | Adverse Events (Number of Participants With Related Adverse Events) | 15 Participants |
| sham-PNS + PT | Adverse Events (Number of Participants With Related Adverse Events) | 14 Participants |