A Comparative Post-marketing Study of Commercially Available Peripheral Nerve Gap Repair Options

A Multicenter, Prospective, Randomized, Comparative Study of Hollow Nerve Conduit and Avance Nerve Graft Evaluating Recovery Outcomes of Nerve Repair in the Hand. (CHANGE)

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00948025

Acronym

CHANGE

Enrollment

Registered

2009-07-29

Start date

2009-06-30

Completion date

2014-12-31

Last updated

2020-12-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Traumatic Nerve Injury

Keywords

Peripheral Nerve Repair, Conduit, AVANCE, Neuroma Resection, Nerve Gap Repair, Digital Nerve Repair, Nerve Graft, Nerve Allograft

Brief summary

This study is a comparison of sensory recovery outcomes following the use of AVANCE Nerve Graft or hollow tube conduit for peripheral nerve gap repairs in the hand.

Detailed description

The CHANGE study is a post-marketing study designed as a prospective, single-blind, randomized, two phase study comparing clinical outcomes of AVANCE Nerve Graft to hollow tube conduits. The first phase (pilot phase) assesses projected differences expected between two treatment groups. The second phase of the study provides comparison data between the two treatment groups. AVANCE Nerve Graft is current regulated in the United States as a 361 HCT/P Tissue for transplantation; not a Drug, Biologic, or Medical Device. Hollow tube conduits are currently regulated in the United States as medical devices.

Interventions

DEVICEHollow tube nerve conduit, synthetic or biosynthetic

Appropriately size matched hollow tube nerve conduit (Neurotube, NeuroLac, NeuraGen, NeuroMatrix, NeuroFlex)

OTHERProcessed Human Nerve Tissue

Implantation of appropriate length of processed human nerve tissue at time of surgery.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Require primary or secondary nerve injury repair with Hollow Nerve Conduit or AVANCE™ in at least 1 digital nerve; * Undergo End to End nerve to nerve graft coaptation on both the proximal and distal portion of the nerve gap in the AVANCE™ group or nerve entubulation in the Hollow Nerve Conduit group; * Be willing to comply with all aspects of the treatment and evaluation schedule over a 12 Month duration; and * Sign and date an IRB-approved written informed consent prior to initiation of any study procedures, including screening procedures.

Exclusion criteria

* Nerve gaps of \< 5 mm or \> 20 mm; * Estimated distance of regeneration of \>125 mm (distance from injury site to sensory target) * Nerve crush or avulsion injuries; * Incomplete nerve transections; * Injury requiring replantation of target digit; * Contralateral digital injuries corresponding to the target digit; * Nerve injuries in the affected limb proximal to the crease of the wrist; * End to side nerve repair; * Injuries with significant vascular damage which may impair adequate perfusion of the target limb; * Subjects who are undergoing treatment with chemotherapy, radiation therapy, or other know treatment which affects the growth of neural and/or vascular system; * Use of bovine collagen based hollow nerve conduit in a subject with known or suspected bovine sensitivity; * Subjects age ≤18 years or ≥70 years; * History neuropathy, diabetic or any other known neuropathy; * Secondary nerve repair \>12 weeks post initial injury; * Currently enrolled in another investigational study; * Expected use of medications during the study that are known to cause peripheral neuropathy; * History or Reynaud's or other disorder known to compromise circulation or sensation in the upper extremity; and * Any subject who at the discretion of the Investigator is not suitable for inclusion in the study.

Design outcomes

Primary

Measure	Time frame	Description
Recovery of Static 2-point Discrimination in the Affected Digit	12 Months	Mean change in static 2-Point Discrimination between baseline and 12 months

Secondary

Measure	Time frame	Description
Semmes-Weinstein Monofilament Assessment	12 months	Percent Change from Baseline of Semmes-Weinstein Monofilament Assessment at Month 12
12-month DASH Core Module Scores	12 months	Summary of Disability of the Arm, Shoulder, and Hand (DASH) scores (Core Module) at Month 12 The Disabilities of the Arm, Shoulder and Hand (DASH) core module questionnaire is a 30-item questionnaire includes 21 physical function items, 6 symptom items, and 3 social/role function items. It is a patient reported questionnaire used to assess physical function and severity of symptoms in patients with musculoskeletal disorders of the upper limb. Each of the items in the DASH use a 5-point Likert scale to assess the corresponding severity or functional parameter. The outcome measure is scored based on the formula (\[sum of n responses)/ - 30 (minimum score\]/1.2 (range of scores ÷100), where n represents the number of completed items. Computed scores range from 0 (no disability) to 100 (most severe disability).
12-month DASH (Work Module) Scores	12 month	Summary of Disability of the Arm, Shoulder, and Hand (DASH) scores (Work Module) at Month 12 The Disabilities of the Arm, Shoulder and Hand (DASH) Work Module questionnaire is a 4-item questionnaire used to identify the job-specific difficulties that workers might experience but which may not affect their activities of daily living. It is a patient reported questionnaire used to assess the impact that musculoskeletal disorders of the upper limb have on a patient's ability to perform work-related tasks. Each of the items in the DASH Work Module use a 5-point Likert scale to assess the corresponding severity or functional parameter. The outcome measure is scored based on the formula (\[sum of n responses)/ - 4 (minimum score\]/0.16 (range of scores ÷100), where n represents the number of completed items. Computed scores range from 0 (no difficulty) to 100 (most severe difficulty).
12- Month DASH (Sports/Performing Arts Module)	12 months	Summary of Disability of the Arm, Shoulder, and Hand (DASH) scores (Sports/Performing Arts Module) at month 12 The Disabilities of the Arm, Shoulder and Hand (DASH) Sports/Performing Arts Module questionnaire is a 4-item questionnaire used to identify the specific difficulties that professional athletes/performing artists might experience but which may not affect their activities of daily living. It is a patient reported questionnaire used to assess the impact that musculoskeletal disorders of the upper limb have on a patient's ability to perform sports or play a musical instrument. Each of the items in the DASH use a 5-point Likert scale to assess the corresponding severity or functional parameter. The outcome measure is scored based on the formula (\[sum of n responses)/ - 4 (minimum score\]/0.16 (range of scores ÷100), where n represents the number of completed items. Computed scores range from 0 (no difficulty) to 100 (most severe difficulty).
Moving 2-point Discrimination	12 months	Percent Change from Baseline of Moving 2-Point Discriminations at Month 12
Thermal Discretion at 12-months	12-month	Summary of Thermal Discretion at Month 12 as determined by the Investigator. Thermal discretion was assessed by applying a hot and/or cold object to the patient's affected digit. Thermal discretion was reported as either present (Yes) or not present (No).
Protective Sensation Present at 12-months	12 months	Summary of Protective Sensation by Month 12 Semmes-Weinstein Monofilament (SWMF) assessment of protective sensation. The gauge of the monofilaments range from 2.83 (normal) to 6.65 (deep pressure sensation only). Protective Sensation Present (SWMF score of 3.61 or better), Protective Sensation Diminished (SWMF score of 4.31-3.84), Protective Sensation Absent (SWMF score of 4.56 or greater).
Functional Recovery Classification (Medical Research Council Evaluation of Sensory Function) at 12-months	12 months	Summary of Functional Recovery Classification (Medical Research Council Evaluation of Sensory Function) at 12-months Patients were assessed for functional recovery of sensation on a scale from S0 to S4 with S0 representing absence of sensibility, S1 representing recovery of deep cutaneous pain sensibility, S2 representing the return of some degree of superficial cutaneous pain and tactile sensibility, S3 representing return of superficial cutaneous pain and tactile sensibility, S3+ representing return of sensibility as in S3 and some recovery of 2-point discrimination (a 2-PD score between 7-15mm), and S4 representing complete recovery of normal sensation as assessed by 2-point discrimination (score between 2-6mm).
Pain at 12-months	12-months	Summary of Pain Assessment using Visual Analogue Scale (VAS) at Month 12 The Visual Analog Scale (VAS) For Pain is a patient reported outcomes scale whereby the patient indicates his/her current pain level by making a mark on a continuous horizontal 10 centimeter (100 millimeter) line. The distance from the 0 millimeter to the patient's mark corresponds to the amount of pain the subject is currently experiencing. VAS for Pain data are recorded as the number of millimeters from the left of the line to the patients mark across the range of 0-100 millimeters, with 0 millimeter representing no pain and 100 millimeters representing the worst pain imaginable.

Countries

United States

Participant flow

Recruitment details

Recruitment began on 22 June 2009 and ended on 23 May 2012.

Participants by arm

Arm	Count
Avance Nerve Graft Commercially available Avance Nerve Graft for repair of nerve gap Processed Human Nerve Tissue: Implantation of appropriate length of processed human nerve tissue scaffold at time of surgery.	14
Hollow Tube Conduit Commercially available hollow tube conduit for repair of nerve gap. Hollow tube nerve conduit, synthetic or biosynthetic: Appropriately size matched hollow tube nerve conduit (Neurotube, NeuroLac, NeuraGen, NeuroMatrix, NeuroFlex)	9
Total	23

Withdrawals & dropouts

Period	Reason	FG000	FG001
Phase 1 (Pilot Phase)	Adverse Event	1	1
Phase 1 (Pilot Phase)	Lost to Follow-up	7	1
Phase 1 (Pilot Phase)	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Hollow Tube Conduit	Avance Nerve Graft	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	9 Participants	14 Participants	23 Participants
Age, Continuous	39 years	45 years	41 years
Region of Enrollment United States	9 participants	14 participants	23 participants
Sex: Female, Male Female	3 Participants	2 Participants	5 Participants
Sex: Female, Male Male	6 Participants	12 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 14	0 / 9
other Total, other adverse events	0 / 14	1 / 9
serious Total, serious adverse events	1 / 14	1 / 9

Outcome results

Primary

Recovery of Static 2-point Discrimination in the Affected Digit

Mean change in static 2-Point Discrimination between baseline and 12 months

Time frame: 12 Months

Population: Number of subjects

Arm	Measure	Value (MEAN)	Dispersion
Avance Nerve Graft	Recovery of Static 2-point Discrimination in the Affected Digit	-65.6 percent change from baseline	Standard Error 5.94
Hollow Tube Conduit	Recovery of Static 2-point Discrimination in the Affected Digit	-31.8 percent change from baseline	Standard Error 10.9

Comparison: 1. P-value comparing static 2-point discrimination per visit derived from mixed linear modeling of longitudinal data.~2. P-Value is based on Mann-Whitney U test.p-value: 0.0433Wilcoxon (Mann-Whitney)

Secondary

12-month DASH Core Module Scores

Summary of Disability of the Arm, Shoulder, and Hand (DASH) scores (Core Module) at Month 12 The Disabilities of the Arm, Shoulder and Hand (DASH) core module questionnaire is a 30-item questionnaire includes 21 physical function items, 6 symptom items, and 3 social/role function items. It is a patient reported questionnaire used to assess physical function and severity of symptoms in patients with musculoskeletal disorders of the upper limb. Each of the items in the DASH use a 5-point Likert scale to assess the corresponding severity or functional parameter. The outcome measure is scored based on the formula (\[sum of n responses)/ - 30 (minimum score\]/1.2 (range of scores ÷100), where n represents the number of completed items. Computed scores range from 0 (no disability) to 100 (most severe disability).

Time frame: 12 months