Phantom Limb Pain, Post-Amputation Pain, Residual Limb Pain, Stump Pain
Conditions
Keywords
Pain, Chronic, Amputation, Phantom Pain, Stump Pain
Brief summary
The purpose of the clinical trial is to learn whether electrical nerve block via the Altius System is a safe and effective treatment for patients with post-amputation pain.
Detailed description
The Altius System is an implanted device designed to electrically block nerve signals and alleviate pain. Use of this device may be associated with providing an effective, mechanism-based yet non-destructive, treatment for managing intractable limb pain in amputees. In a given patient, the Altius System will be deemed effective if treatment results in 50% reduction of pain score for more than 50% of all pain episodes.
Interventions
DEVICEAltius
Electrical signal
Sponsors
Neuros Medical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age ≥ 21 years old * Unilateral amputated leg ≥ 12 months * Chronic post amputation pain ≥ 6 months * Pain episodes typically lasting ≥ 60 minutes * Stable drug regimen ≥ 4 weeks * No changes to medications or prosthesis for 3-month primary study period Key
Exclusion criteria
* Implanted with an active implantable medical device (i.e. pacemaker) * Confounding source of pain that interferes with reporting of limb pain * Uncontrolled diabetes * Spasticity preventing full range of motion of involved side * Extremely short stump; sits on end * Untreated psychological condition (i.e. borderline personality) * Condition requiring MRI studies or diathermy after device implant * Life expectancy of less than 24 months * Progressive neurological disease (i.e. multiple sclerosis) * Subjects with active local or systemic infection or immunocompromised
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline | Randomized Testing Window (Month-1 to Month-3 post implant, 2 Month duration) | Demonstration of 50% reduction in a Numerical Rating Scale (NRS; 0-10 Scale; with 10 being the highest pain imaginable) pain score from pre-treatment to post-treatment for more than 50% of all pain episodes. Study success will be determined by a superiority test on the difference between responder rates in the Test group (those receiving the treatment) and Control group (those who do not receive treatment). |
| Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events | From screening injection visit through 3 months post implant | Incidence of all serious adverse events including serious adverse device events and unanticipated adverse device events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Effectiveness: Pain Interference to Activities of Daily Living (ADL | 12 months post implant | Brief Pain Inventory summary score compared at Month 3, Month 6 and Month 12 to Baseline. |
| Secondary Effectiveness: Health-related Quality of Life (HR-QOL) | 12 months post implant | EQ-5D summary index, SF-12 physical component and mental component summary compared at Month 3, Month 6 and Month 12 to Baseline. |
| Secondary Effectiveness: Pain Relief After 2 Hours | 12 months post implant | Average percent change of pain intensity from before treatment, 30 minutes post treatment, and 2 hours post treatment |
| Secondary Safety | 12 months post implant | Incidence of all Non-Serious Adverse Events, including Non-Serious Adverse Events, Non-Serious Adverse Device Events, and Unanticipated (Non-Serious) Adverse Device Events from the time of consent through 12 months post implant. |
| Secondary Effectiveness: Patient Global Impression of Change (PGIC) | 12 months post implant | Comparison of Patient Global Impression of Change across the Month 3, Month 6 and Month 12 office visits |
| Secondary Effectiveness: Pain Medication Use | 12 months post implant | Average morphine equivalent dose per day over two weeks compared at Month 3, Month 6 and Month 12 to Baseline. |
Countries
United States
Participant flow
Pre-assignment details
Subjects were required to fulfill all eligibility requirements, including lidocaine injection screening. Eligible subjects underwent study device implant and activation prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Test Treatment Self-initiated high frequency bioelectric nerve block delivered to the nerve by Altius. | 85 |
| Active Sham Control Treatment Self-initiated non-therapeutic electrical signal delivered to the nerve by Altius. | 85 |
| Total | 170 |
Baseline characteristics
| Characteristic | Test Treatment | Total | Active Sham Control Treatment |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 12.21 | 58.0 years STANDARD_DEVIATION 12.35 | 57.9 years STANDARD_DEVIATION 12.57 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants | 167 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Level of Amputation Above knee (AKA) | 38 Participants | 73 Participants | 35 Participants |
| Level of Amputation Below knee (BKA) | 47 Participants | 97 Participants | 50 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 22 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 66 Participants | 137 Participants | 71 Participants |
| Sex: Female, Male Female | 34 Participants | 68 Participants | 34 Participants |
| Sex: Female, Male Male | 51 Participants | 102 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 85 | 2 / 85 |
| other Total, other adverse events | 34 / 85 | 34 / 85 |
| serious Total, serious adverse events | 35 / 85 | 35 / 85 |
Outcome results
Primary
Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline
Demonstration of 50% reduction in a Numerical Rating Scale (NRS; 0-10 Scale; with 10 being the highest pain imaginable) pain score from pre-treatment to post-treatment for more than 50% of all pain episodes. Study success will be determined by a superiority test on the difference between responder rates in the Test group (those receiving the treatment) and Control group (those who do not receive treatment).
Time frame: Randomized Testing Window (Month-1 to Month-3 post implant, 2 Month duration)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Test Treatment | Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline | 21 Participants |
| Active Sham Control Treatment | Primary Effectiveness Endpoint: Reduction of Pain Level by 50% From Baseline | 6 Participants |
p-value: 0.00295% CI: [0.07, 0.283]Regression, Logistic
Primary
Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events
Incidence of all serious adverse events including serious adverse device events and unanticipated adverse device events.
Time frame: From screening injection visit through 3 months post implant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test Treatment | Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events | All Serious Adverse Events (SAE) | 24 Participants |
| Test Treatment | Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events | Serious Adverse Device Effect (SADE) | 3 Participants |
| Test Treatment | Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events | Unanticipated Adverse Device Effect (UADE) | 0 Participants |
| Active Sham Control Treatment | Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events | All Serious Adverse Events (SAE) | 19 Participants |
| Active Sham Control Treatment | Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events | Serious Adverse Device Effect (SADE) | 5 Participants |
| Active Sham Control Treatment | Primary Safety Endpoint: Incidence of Reported and Adjudicated Serious Adverse Events | Unanticipated Adverse Device Effect (UADE) | 0 Participants |
Secondary
Secondary Effectiveness: Health-related Quality of Life (HR-QOL)
EQ-5D summary index, SF-12 physical component and mental component summary compared at Month 3, Month 6 and Month 12 to Baseline.
Time frame: 12 months post implant
Secondary
Secondary Effectiveness: Pain Interference to Activities of Daily Living (ADL
Brief Pain Inventory summary score compared at Month 3, Month 6 and Month 12 to Baseline.
Time frame: 12 months post implant
Secondary
Secondary Effectiveness: Pain Medication Use
Average morphine equivalent dose per day over two weeks compared at Month 3, Month 6 and Month 12 to Baseline.
Time frame: 12 months post implant
Secondary
Secondary Effectiveness: Pain Relief After 2 Hours
Average percent change of pain intensity from before treatment, 30 minutes post treatment, and 2 hours post treatment
Time frame: 12 months post implant
Secondary
Secondary Effectiveness: Patient Global Impression of Change (PGIC)
Comparison of Patient Global Impression of Change across the Month 3, Month 6 and Month 12 office visits
Time frame: 12 months post implant
Secondary
Secondary Safety
Incidence of all Non-Serious Adverse Events, including Non-Serious Adverse Events, Non-Serious Adverse Device Events, and Unanticipated (Non-Serious) Adverse Device Events from the time of consent through 12 months post implant.
Time frame: 12 months post implant