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

Cubital Tunnel Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04647058
• Other study ID #: 2020P003713
• Status: Withdrawn
• Phase: N/A
• Start date: April 5, 2021
• Est. completion date: January 27, 2022

Study information

• Verified date: January 2022
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 27, 2022
• Est. primary completion date: January 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Charcot-Marie-Tooth Disease
• Cubital Tunnel Syndrome
• Hereditary Sensory and Motor Neuropathy
• Nerve Compression Syndromes
• Syndrome
• Ulnar Claw
• Ulnar Nerve Compression
• Ulnar Nerve Entrapment
• Ulnar Nerve Entrapment at Elbow
• Ulnar Nerve Entrapment Syndrome
• Ulnar Nerve Palsy
• Ulnar Neuropathies

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (11)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Arriyan S. Dowlatshahi, Brandon E. Earp, Carl M. Harper, Christian E. Sampson, George S. M. Dyer, Lydia A. Helliwell, Matthew J. Carty, Philip Blazar, Simon G. Talbot, Tamara D. Rozental

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subterminal key pinch strength	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	Patient-Rated Ulnar Nerve Evaluation (PRUNE) score	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
Secondary	Disabilities of the Arm, Shoulder and Hand (DASH) score	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
Secondary	MRC forearm pronation strength	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