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

NCT ID: NCT04647058

Last Updated: 2022-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-05

Study Completion Date

2022-01-27

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cubital Tunnel Syndrome Ulnar Nerve Compression Ulnar Nerve Palsy Ulnar Nerve Entrapment Ulnar Nerve Entrapment at Elbow Ulnar Nerve Entrapment Syndrome Ulnar Neuropathies Ulnar Claw

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Cubital tunnel release

Intervention Type PROCEDURE

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.

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.

Group Type EXPERIMENTAL

Supercharged end-to-side (SETS) nerve transfer

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Philip Blazar

UNKNOWN

Sponsor Role collaborator

Matthew J. Carty

UNKNOWN

Sponsor Role collaborator

Arriyan S. Dowlatshahi

UNKNOWN

Sponsor Role collaborator

George S. M. Dyer

UNKNOWN

Sponsor Role collaborator

Brandon E. Earp

UNKNOWN

Sponsor Role collaborator

Carl M. Harper

UNKNOWN

Sponsor Role collaborator

Lydia A. Helliwell

UNKNOWN

Sponsor Role collaborator

Tamara D. Rozental

UNKNOWN

Sponsor Role collaborator

Christian E. Sampson

UNKNOWN

Sponsor Role collaborator

Simon G. Talbot

UNKNOWN

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dafang Zhang, M.D.

Instructor in Orthopaedic Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dafang Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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Barbour J, Yee A, Kahn LC, Mackinnon SE. Supercharged end-to-side anterior interosseous to ulnar motor nerve transfer for intrinsic musculature reinnervation. J Hand Surg Am. 2012 Oct;37(10):2150-9. doi: 10.1016/j.jhsa.2012.07.022.

Reference Type BACKGROUND
PMID: 23021177 (View on PubMed)

Jarvie G, Hupin-Debeurme M, Glaris Z, Daneshvar P. Supercharge End-to-Side Anterior Interosseous Nerve to Ulnar Motor Nerve Transfer for Severe Ulnar Neuropathy: Two Cases Suggesting Recovery Secondary to Nerve Transfer. J Orthop Case Rep. 2018 Sep-Oct;8(5):25-28. doi: 10.13107/jocr.2250-0685.1194.

Reference Type BACKGROUND
PMID: 30740369 (View on PubMed)

Davidge KM, Yee A, Moore AM, Mackinnon SE. The Supercharge End-to-Side Anterior Interosseous-to-Ulnar Motor Nerve Transfer for Restoring Intrinsic Function: Clinical Experience. Plast Reconstr Surg. 2015 Sep;136(3):344e-352e. doi: 10.1097/PRS.0000000000001514.

Reference Type BACKGROUND
PMID: 26313839 (View on PubMed)

Dengler J, Dolen U, Patterson JMM, Davidge KM, Kahn LC, Yee A, Mackinnon SE. Supercharge End-to-Side Anterior Interosseous-to-Ulnar Motor Nerve Transfer Restores Intrinsic Function in Cubital Tunnel Syndrome. Plast Reconstr Surg. 2020 Oct;146(4):808-818. doi: 10.1097/PRS.0000000000007167.

Reference Type BACKGROUND
PMID: 32590517 (View on PubMed)

Dunn JC, Gonzalez GA, Fernandez I, Orr JD, Polfer EM, Nesti LJ. Supercharge End-to-Side Nerve Transfer: Systematic Review. Hand (N Y). 2021 Mar;16(2):151-156. doi: 10.1177/1558944719836213. Epub 2019 Mar 29.

Reference Type BACKGROUND
PMID: 30924361 (View on PubMed)

Koriem E, El-Mahy MM, Atiyya AN, Diab RA. Comparison Between Supercharged Ulnar Nerve Repair by Anterior Interosseous Nerve Transfer and Isolated Ulnar Nerve Repair in Proximal Ulnar Nerve Injuries. J Hand Surg Am. 2020 Feb;45(2):104-110. doi: 10.1016/j.jhsa.2019.11.005. Epub 2019 Dec 20.

Reference Type BACKGROUND
PMID: 31866151 (View on PubMed)

MacDermid JC, Grewal R. Development and validation of the patient-rated ulnar nerve evaluation. BMC Musculoskelet Disord. 2013 Apr 26;14:146. doi: 10.1186/1471-2474-14-146.

Reference Type BACKGROUND
PMID: 23617407 (View on PubMed)

Bertelli JA. Subterminal key pinch dynamometry: a new method to quantify strength deficit in ulnar nerve paralysis. J Hand Surg Eur Vol. 2020 Oct;45(8):813-817. doi: 10.1177/1753193420919283. Epub 2020 Apr 29.

Reference Type BACKGROUND
PMID: 32349609 (View on PubMed)

Head LK, Zhang ZZ, Hicks K, Wolff G, Boyd KU. Evaluation of Intrinsic Hand Musculature Reinnervation following Supercharge End-to-Side Anterior Interosseous-to-Ulnar Motor Nerve Transfer. Plast Reconstr Surg. 2020 Jul;146(1):128-132. doi: 10.1097/PRS.0000000000006903.

Reference Type BACKGROUND
PMID: 32590654 (View on PubMed)

Other Identifiers

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2020P003713

Identifier Type: -

Identifier Source: org_study_id

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