Peripheral Nerve Injury (PNI), Peripheral Nerve Injury Upper Limb
Conditions
Keywords
Transected Nerves, Requiring Surgical Repair, Upper Extremity
Brief summary
NTX-001 is a single use surgical product intended for use in conjunction with standard suture neurorrhaphy of severed nerves in patients between 18 and 80.
Detailed description
NTX-001 has been developed as a surgical product to be used in conjunction with standard suture neurorrhaphy of a severed nerve. Use of NTX-001 is intended to safely accelerate the often slow and diminished return of function in repaired nerves. It often takes months and/or years to determine if function will be restored. By that point, restoration is often incomplete and can result in lifelong motor and/or sensory deficits. By reconnecting (PEG-fusion) a substantial number of axons within a severed nerve, the degeneration-regeneration cycle and subsequent atrophy may be reduced or even prevented for those axons and their targets, respectively. NTX-001 (PEG-fusion) has the potential to avoid the consequences of protracted denervation of distal target tissues by eliminating the period of total denervation thus reducing the time to stable recovery and providing greater innervation to affected tissues.
Interventions
COMBINATION_PRODUCTNTX-001 (PEG-Fusion)
One time use surgical product, 3 solutions applied topically, in sequence, to the peripheral nerve repair site, in conjunction with standard suture neurorrhaphy.
Sponsors
Neuraptive Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
All study personnel involved in the surgical procedure will be unblinded. Patient, Care Providers and outcomes evaluators will be blinded.
Intervention model description
Treatment vs. Standard of Care
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* The subject has voluntarily agreed to participate in this study and has signed an Institutional Review Board (IRB) approved informed consent form. * The subject is between eighteen (18) and eighty (80) years of age. * The subject has clinical evidence of a Sunderland's 4th degree (Class II) or 5th degree (Class III) nerve transection(s) that has resulted in upper extremity nerve impairment that requires surgical treatment.
Exclusion criteria
* Subjects whose nerve repair will occur greater than 48 hours after nerve transection. * Subjects requiring nerve repair involving an autograft, allograft or conduit(s). * Subjects with multiple transected nerve injuries are allowed into the study only if all injuries are amenable to direct repair. * Subjects who, in the judgement of the investigator, are not likely to demonstrate meaningful recovery within a reasonable time frame during follow up due to significant muscle atrophy or other morbidity. * The subject's injury is a result of a suicide attempt or self- harm. * The subject has documented history or clinical signs of any condition where NTX-001 might not prove beneficial (e.g., systemic neuromuscular disease, systemic neurological deficit, or other treatments known to affect the growth and/or physiology of the neural and vascular system). * The subject has a known allergy to polyethylene glycol (PEG) or human grade silicone. * The subject is pregnant or breastfeeding. * The subject is currently enrolled in another investigational study or has participated in an investigational study within 30 days prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Michigan Hand Questionnaire (MHQ) Two Domain Score (ADL and Pain) | Screening Visit, Week 24 | The subject will complete the MHQ questionnaire at Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48. A measure of the mean of MHQ in the Two Domains, Activities of Daily Living and Pain Scores, at Week 24 in the NTX-001 group as compared to Standard of Care (SoC). In the ADL subdomain, a higher component score indicates better function. In the Pain subdomain, a higher component score indicates greater pain. A total MHQ score of 100 is considered the best functional score. |
| Safety - Columbia-Suicide Severity Rating Scale | Screening Visit, Weeks 4, 12, and 48 | The Columbia-Suicide Severity Rating Scale (C-SSRS) is a suicide risk assessment tool. The C-SSRS tool asks; whether and when the subject has had a thought about suicide (ideation); what actions they might have taken and what they did to prepare for suicide; whether and when they attempted suicide or began a suicide attempt that was either interrupted by another person or stopped of their own volition. The answers identify whether someone is at risk for suicide, assessing the severity and immediacy of that risk, and gauging the level of support that the person needs. The first assessment is done by study staff at screening. Subsequent assessments will be completed by the subject at Weeks 4, 12, and 48. A score of 0 indicates no risk, 1-2 indicates low risk, and 3+ indicates moderate to high risk. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative CheckPoint® Stimulation. | In Operating Room | A CheckPoint® Stimulator will be used intra-operatively to detect immediate reconnection of severed peripheral nerves (axons) in mixed-motor nerves only. The measures include in response of direct nerve stimulation, proximally and distally to suture site. |
| MHQ Total Score | Screening Visit; Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48 | The MHQ quantifies different impairments between the subjects in uninjured and involved upper extremities. A general survey of hand function includes twenty-five items for the right and the left hand, as well as questions for both hands. Questions regarding function specifically refer to the impact of the involved hand and/or wrist on the activity which presumably takes all joints of the upper extremity into account. The overall questionnaire is scored from 0 to 100, with 100 being the optimal score. |
| Time to Return to Function | Screening Visit, Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48. | Achievement of seventy-five (75)% function in the combined ADL and pain MHQ domain scores. The Activities of Daily Living component evaluates the ability to perform specific tasks using either hand or both hands together. The Pain subdomain addresses the frequency and intensity of pain in both the right and left hands/wrists, along with its impact on sleep and daily activities, and the emotional distress it causes. The overall questionnaire is scored from 0 to 100, with 100 being the optimal score. |
| Change in NPRS | Screening Visit, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 30, 36, 42, and 48 | The NPRS is used to assess for pain and to determine pain intensity. The NPRS is an 11-point scale scored from 0-10: 1) "0" = no pain 2) "10" = the most intense pain imaginable. The average of the 3 ratings is used to represent the subject's level of pain over the previous 24 hours. |
| Semmes Weinstein Monofilament Test (SWMT) | Weeks 2, 4, 8, 12, 24, 36, 48. | SWMT provides information on protective sensation, the rigorous system can detect relatively minor differences in sensory function, and changes will occur early in nerve injury. The assessment tool consists of a set of monofilaments that vary in thickness and diameter, the gradient forces of these monofilaments that subjects\' can feel, range from 0.086 gm to 0.448gm. The normal value in the hand is in the range of the green filament (1.65 to 2.83 mN). |
| MHQ Two Domain Score | Screening Visit; Weeks 2, 4, 6, 8, 10, 12, 16, 20, 30, 36, 42, 48 | The Activities of Daily Living component evaluates the ability to perform specific tasks using either hand or both hands together. The Pain subdomain addresses the frequency and intensity of pain in both the right and left hands/wrists, along with its impact on sleep and daily activities, and the emotional distress it causes. The raw scale score for each of the 6 scales is the sum of the responses of each scale item. The raw score is converted to a score range from 0 to 100. 100 being the best. |
| Change from Week 2 in MHQ Two Domain Score | Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48. | The Activities of Daily Living component evaluates the ability to perform specific tasks using either hand or both hands together. The Pain subdomain addresses the frequency and intensity of pain in both the right and left hands/wrists, along with its impact on sleep and daily activities, and the emotional distress it causes. The raw scale score for each of the 6 scales is the sum of the responses of each scale item. The raw score is converted to a score range from 0 to 100. 100 being the best. |
| Medical Research Council Classification (MRCC) Sensory Score | Weeks 2, 4, 8, 12, 24, 36, and 48. | The scale is commonly used including 2 Point Discrimination for grading the sensory outcome after peripheral nerve surgery. This scale is categorized into S0-S4: S0 is the absence of sensibility; S1 is the recovery of deep cutaneous pain; S2 is the return of superficial cutaneous pain and some degree of tactile sensibility; S3 is the return of superficial cutaneous pain and tactile sensibility without over response; and S4 is the complete recovery. |
| Medical Research Council Classification (MRCC) Motor Score | Weeks 2, 4, 8, 12, 24, 36, 48 | This assessment is conducted on mixed motor nerve injuries only. Strength can best be assessed by isolating an individual muscle group and comparing power with that of the subject. It can be conducted to assess larger muscles or muscle groups as well as intrinsic muscles of the hand. Measuring the difference between the affected limb and the contralateral limb. 0/5 is no muscle activation whatsoever; 1/5 is muscle activation without limb movement; 2/5 implies that the limb can be moved only when gravity is taken out of the equation; 3/5 means that the subject can overcome gravity but not resistance;• 4/5 (or 4+ or 4-) implies weakness with enough strength to overcome varying degrees of physical resistance; 5/5 is full strength. |
| Change from Baseline (W2) in Numeric Pain Rating Scale (NPRS) | Weeks 2, 24. | The NPRS is used to assess for pain and to determine pain intensity. The NPRS is an 11-point scale scored from 0-10: 1) "0" = no pain 2) "10" = the most intense pain imaginable. The average of the 3 ratings is used to represent the subject's level of pain over the previous 24 hours. |
| Patient Global Impression of Change Score | Weeks 2, 4, 6, 8, 10, 12, 16, 20, 30, 36, 42, and 48 | This scale evaluates all aspects of patients; health and assesses if there has been an improvement or decline in clinical status. PGIC is a 7-point scale depicting a subjects rating of overall improvement. The subject rates their change as "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," or "very much worse." |
| Change in Total MHQ Score | Screening Visit; Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42, and 48. | The MHQ quantifies different impairments between the subjects uninjured and involved upper extremities. It was designed as a general survey of hand function and includes twenty-five items for the right and the left hand, as well as questions for both hands. Furthermore, questions regarding function specifically refer to the impact of the involved hand and/or wrist on the activity which presumably takes all joints of the upper extremity into account. The overall questionnaire is scored from 0 to 100, with 100 being the optimal score. |
| Change from Baseline in Patient Global Impression of Severity Score (PGIS) | Screening Visit; Weeks 2, 4, 6, 8, 10, 12, 16, 20, 24, 30, 36, 42 and 48. | The PGIS is a single question asking the subject to rate the severity of the injury from the last visit. PGIS is a scale depicting a subject's rating of overall severity. The subject scores their perception of severity as "none," "mild," "moderate," "severe," or "very severe." |
Countries
United States
Contacts
CONTACTSeth Schulman, MD
CONTACTKristen Olszyk, MS
STUDY_DIRECTORSeth Schulman, MD
Neuraptive Therapeutics Inc.
Outcome results
None listed