Randomized Trial of Supercharged End-to-Side Anterior Interosseous Nerve Transfer for Severe Cubital Tunnel Syndrome

January 27, 2022 updated by: Dafang Zhang, M.D., Brigham and Women's Hospital

Randomized Controlled Trial of Supercharged End-to-Side (SETS) Anterior Interosseous Nerve Transfer for Severe Cubital Tunnel Syndrome

Functional motor recovery distal to a peripheral nerve lesion is predicated upon time to reinnervation of the motor end plate and the number of regenerate axons that reach the target. Supercharged end-to-side (SETS) transfer of the anterior interosseous nerve to the motor fascicle of the ulnar nerve at the level of the distal forearm has been proposed as an adjunct procedure in severe cubital tunnel syndrome to augment motor recovery of the ulnar-innervated intrinsic muscles. Multiple Level IV Therapeutic studies and a systematic review of Level IV Therapeutic studies have reported favorable clinical and electrodiagnostic outcomes following SETS for cubital tunnel syndrome, with low rates of complications. However, in the absence of controls, it remains unclear what proportion of the observed intrinsic motor recovery is attributable to the SETS procedure. The objective of this randomized trial is to compare the results of ulnar nerve decompression with or without SETS for severe cubital tunnel syndrome.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Null hypothesis: Ulnar nerve decompression with or without supercharged end-to-side (SETS) anterior interosseous nerve transfer for McGowan classification stage III cubital tunnel syndrome results in similar ulnar intrinsic motor recovery.

Background Functional motor recovery distal to a peripheral nerve lesion is predicated upon time to reinnervation of the motor end plate and the number of regenerate axons that reach the target. Supercharged end-to-side (SETS) transfer of the anterior interosseous nerve to the motor fascicle of the ulnar nerve at the level of the distal forearm has been proposed as an adjunct procedure in severe cubital tunnel syndrome to augment motor recovery of the ulnar-innervated intrinsic muscles. The proposed mechanism of action of SETS is twofold: (1) "babysitting" the motor end plates until native regenerate axons reach their target, and (2) augmented partial recovery through axonal growth through the new pathway.

Multiple Level IV Therapeutic studies and a systematic review of Level IV Therapeutic studies have reported favorable clinical and electrodiagnostic outcomes following SETS for cubital tunnel syndrome, with low rates of complications. However, in the absence of controls, it remains unclear what proportion of the observed intrinsic motor recovery is attributable to the SETS procedure. Koriem et al. recently published a prospective, randomized comparative study of ulnar nerve repair with or without SETS for proximal ulnar nerve injuries and demonstrated superior intrinsic recovery and claw correction with the SETS procedure. Prospective, randomized trials of SETS for severe cubital tunnel syndrome are needed.

The objective of this study is to compare the results of ulnar nerve decompression with or without SETS for severe cubital tunnel syndrome. In this study, severe cubital tunnel syndrome is defined as McGowan classification stage III disease (sensory deficits, motor deficits, and the presence of intrinsic atrophy).

Methods Patient Selection A prospective, randomized controlled trial will be conducted at two participating institutions: Brigham and Women's Hospital and Beth Israel Deaconess Medical Center. Inclusion criteria are patients 18 years of age or older indicated for surgical treatment of severe cubital tunnel syndrome at one of the two participating institutions. Inclusion criteria furthermore includes a preoperative nerve conduction study and electromyography documenting ulnar neuropathy at the elbow with present fibrillations and positive sharp waves in the FDI or ADM within one year of surgery. Severe cubital tunnel syndrome is defined in this study as McGowan classification stage IIB or III disease (sensory deficits, motor deficits, and the presence of intrinsic atrophy). Exclusion criteria include ulnar nerve transections, traumatic brachial plexus injuries, brachial plexus neuritis (e.g. Parsonage-Turner), cervical radiculopathy, primary motor neuropathy (e.g. Charcot-Marie-Tooth), prior cubital tunnel surgery, and oncologic etiologies of ulnar nerve compression. Exclusion criteria additionally include patients who are not capable of decision-making or are unable to understand the study procedures. Non-English speaking patients are excluded since our secondary outcome variables may not have been translated and validated in other language(s). Comorbid carpal tunnel syndrome, concomitant carpal tunnel release, comorbid diabetes mellitus, and internervous connections such as Martin-Gruber connections are not criteria for exclusion.

Randomization Patients included in this study will be randomly assigned to the SETS group or the control group with a 1:1 enrollment ratio. A computerized random number generator will be used for allocation, which will be concealed by sequentially numbered, sealed, opaque envelopes opened after patient consent and enrollment.

Treatment The control group will undergo cubital tunnel release in situ. In cases of preoperative or intraoperative ulnar nerve instability, anterior transposition of the ulnar nerve will be performed. A soft dressing will be applied for in situ decompressions. A posterior elbow plaster splint will be used for anterior transpositions for 2 weeks. Patients will receive formal occupational therapy for scar massage, range of motion, and progressive intrinsic strengthening starting at 2 weeks postoperatively for 6 weeks duration.

The SETS group will undergo the same procedure as described above, with the addition of the SETS procedure as previously described.1 Decompression of Guyon's canal during the SETS procedure is at the discretion of the treating surgeon. In addition to the aforementioned elbow dressing, a neutral wrist splint will be used for 2 weeks. Patients will receive formal occupational therapy for scar massage, range of motion, and motor re-education consisting of repetitive forearm pronation exercises starting at 2 weeks postoperatively for 6 weeks duration.

Data collection

Primary outcome variable:

Subterminal key pinch strength (kg) - continuous Time points: 0, 3 months, 6 months, 12 months, 18 months

Secondary outcome variables:

Patient-Rated Ulnar Nerve Evaluation (PRUNE) score - continuous, non-parametric Disabilities of the Arm, Shoulder and Hand (DASH) score - continuous, non-parametric MRC forearm pronation strength in elbow flexion and extension - ordinal, non-parametric Time points: 0, 3 months, 6 months, 12 months, 18 months

Explanatory variables:

Age - continuous, non-parametric Sex - dichotomous Dominant hand - dichotomous BMI - continuous, parametric Diabetes mellitus - dichotomous Smoking status - dichotomous Worker's Compensation status - dichotomous Duration of symptoms at presentation (months) - continuous, non-parametric Preoperative NCS SNAP - continuous, parametric Preoperative NCS CMAP - continuous, parametric Guyon's canal decompression - dichotomous

Statistical analysis An a priori power calculation was performed. Assuming a 1:1 enrollment ratio and a mean subterminal key pinch strength of 4 kg (standard deviation 1 kg), a sample size of 32 (16 patients in each group) has 80% power to detect a 1 kg difference in subterminal key pinch strength between groups.

Descriptive statistics will be calculated for the study cohorts. The student's t-test will be used to compare the primary outcome variable and the Mann-Whitney U test will be used to compare the secondary outcome variables between the SETS group and the control group.

The investigators will use bivariate analysis to screen for factors associated with poorer outcome in the SETS group and in the control group. Variables that meet our inclusion criteria (p < 0.1) will be included in a multiple regression model to assess for independent factors associated with poorer outcomes following the study procedures.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02115
        • Beth Israel Deaconess Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients 18 years of age or older
  • Severe cubital tunnel syndrome is defined in this study as McGowan classification stage IIB or III disease (sensory deficits, motor deficits, and the presence of intrinsic atrophy)
  • Indicated for surgical treatment of severe cubital tunnel syndrome at one of the two participating institutions
  • Preoperative nerve conduction study and electromyography documenting ulnar neuropathy at the elbow with present fibrillations and positive sharp waves in the FDI or ADM within one year of surgery

Exclusion Criteria:

  • Ulnar nerve transections
  • Traumatic brachial plexus injuries
  • Brachial plexus neuritis (e.g. Parsonage-Turner)
  • Cervical radiculopathy
  • Primary motor neuropathy (e.g. Charcot-Marie-Tooth)
  • Prior cubital tunnel surgery
  • Oncologic etiologies of ulnar nerve compression
  • Patients who are not capable of decision-making or are unable to understand the study procedures
  • Non-English speaking patients are excluded since our secondary outcome variables may not have been translated and validated in other language(s).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cubital tunnel release
The control group will undergo cubital tunnel release in situ. In cases of preoperative or intraoperative ulnar nerve instability, anterior transposition of the ulnar nerve will be performed.
Procedure: Cubital tunnel release
The control group will undergo cubital tunnel release in situ. In cases of preoperative or intraoperative ulnar nerve instability, anterior transposition of the ulnar nerve will be performed.
Experimental: Supercharged end-to-side (SETS) nerve transfer
The SETS group will undergo the same procedure as described above, with the addition of the SETS procedure consisting of a end-to-side transfer of the anterior interosseous nerve to the ulnar nerve motor branch. Decompression of Guyon's canal during the SETS procedure is at the discretion of the treating surgeon.
Procedure: Supercharged end-to-side (SETS) nerve transfer
The SETS group will undergo the same procedure as described above, with the addition of the SETS procedure consisting of a end-to-side transfer of the anterior interosseous nerve to the ulnar nerve motor branch. Decompression of Guyon's canal during the SETS procedure is at the discretion of the treating surgeon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subterminal key pinch strength
Time Frame: 18 months
The primary outcome variable of this study is subterminal key pinch strength assessed by dynanometer measured in kg. Subterminal key pinch strength is a direct assessment of ulnar-innervated muscle strength.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient-Rated Ulnar Nerve Evaluation (PRUNE) score
Time Frame: 18 months
The PRUNE score is a validated patient-reported outcome measure of ulnar nerve function. The total PRUNE score ranges from 0 to 100, with 0 denoting no symptoms and 100 denoting the worst possible symptoms.
18 months
Disabilities of the Arm, Shoulder and Hand (DASH) score
Time Frame: 18 months
The DASH score is a validated patient-reported outcome measure of upper extremity function. The total DASH score ranges from 0 to 100, with 0 denoting no disability and 100 denoting the most severe disability.
18 months
MRC forearm pronation strength
Time Frame: 18 months
The MRC forearm pronation strength is a commonly used physician-rated scoring system for muscle strength on a 0 to 5 scale and will be used to assess donor deficits from an anterior interosseous nerve transfer, with 0 denoting no strength and 5 denoting full strength.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Philip Blazar
Matthew J. Carty
Arriyan S. Dowlatshahi
George S. M. Dyer
Brandon E. Earp
Carl M. Harper
Lydia A. Helliwell
Tamara D. Rozental
Christian E. Sampson
Simon G. Talbot

Investigators

  • Principal Investigator: Dafang Zhang, MD, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 5, 2021

Primary Completion (Actual)

January 27, 2022

Study Completion (Actual)

January 27, 2022

Study Registration Dates

First Submitted

November 16, 2020

First Submitted That Met QC Criteria

November 21, 2020

First Posted (Actual)

November 30, 2020

Study Record Updates

Last Update Posted (Actual)

February 10, 2022

Last Update Submitted That Met QC Criteria

January 27, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020P003713

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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