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Nerve InjuryPhase 1/2NCT05242302

AIN Transfer for Cubital Tunnel Syndrome

A Phase 1/2 study testing nerve transfer in people with Nerve Injury and Surgery, run by University of Alberta at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Ulnar nerve compressive injury due to cubital tunnel syndrome is very common. Because of the long distance to the target muscles in the hand, functional outcome in severe cases even with decompression surgery is often poor. Therefore, alternative treatment options are much needed. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Nerve Injury, Surgery
What is being tested?
nerve transfer
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
1 siteCanada
Study dates
1 Jan 2019to 28 Feb 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patients (age > 18)
  • Symptoms and signs indicative of cubital tunnel syndrome
  • Markedly depleted motor unit number estimate in the ulnar intrinsic hand muscles > 2 SD below the mean

Who cannot join

  • Other co-existing neurological or musculoskeletal conditions affecting hand function
  • Cognitive impairments rendering patient unable to follow instructions to perform functional tasks
  • Unwilling to consent to the study

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • University of Alberta

    Edmonton, Alberta, T6G 2E1

Other trials in Canada

About this study

Official title: Efficacy of End-to-Side Nerve Transfer for Patients With Severe Cubital Tunnel Syndrome

Ulnar nerve compressive injury due to cubital tunnel syndrome is very common. Because of the long distance to the target muscles in the hand, functional outcome in severe cases even with decompression surgery is often poor. Therefore, alternative treatment options are much needed. Recently, anterior interosseous nerve reverse end to side (RETS) transfer to the ulnar nerve above the wrist has gained popularity. However, whether a substantial portion of motor axons in the donor nerve are indeed capable of breaching the connective tissues in the ulnar nerve to reach the target muscles in the hand remains untested. To answer this crucial question, in this study the investigators plan to recruit 60 cubital tunnel syndrome patients with marked motor axonal loss who will undergo the RETS procedure. Motor unit number estimation will be done on the ulnar and anterior interosseous nerves at baseline and repeated at 3 and 6 months post operatively. Hand motor function and disability scores will also be tested at the same time points. Given the importance of this critical question and the potential utilities of distal nerve transfers, this should be a worthwhile effort.

Read the detailed description

Introduction Peripheral nerve trauma especially through compressive injury is very common. Of these, ulnar neuropathy at the elbow is the second most prevalent. In severe cases, functional outcomes even with surgery are often poor. Principle reasons being that the ulnar nerve innervates a large number of intrinsic hand muscles. At an average of 350 mm from the site of injury to the target muscles, the distance is very long, Although peripheral nerve fibres have the ability to regenerate, it is very slow at only 1 mm/day. That would translate to a year for the regenerating fibres to reach the hand. With the favorable condition in the distal stump and target muscles to regrowth rapidly declining over time, few axons will successfully reach target. Therefore, alternative methods of surgical treatments are being sought to circumvent this major hurdle.

Rationale and purpose One potentially promising alternative is through distal nerve transfer by using a terminal branch of the anterior interosseous nerve (AIN) to the pronator quadratus muscle and coapt it to the ulnar nerve close to the wrist. That would greatly shorten the distance to target by 200 mm or more. By approximating the end of the AIN donor stump to the side of the ulnar nerve through an eipneurial window (termed reverse end to side or RETS) transfer, it allows preservation of the integrity of the ulnar nerve fibres thus providing a conduit for the regenerating native axons to reach the hand. While this concept is theoretically appealing and has gained increasing popularity in clinical practice, a crucial question of central importance remains answered: Can the AIN donor axons indeed breach the ulnar nerve trunk and reinnervate the hand muscles? Aside from testing the central premise of RETS, it would be important to know the exact magnitude of reinnervation that can be achieved from the donor nerve through this procedure.

With the above rationale in mind, the objective of this proposal is to test the hypothesis that reinnervation of ulnar intrinsic hand muscles by the AIN can be achieved through the RETS procedure. This will be done through quantifying the amount of innervation by the AIN donor nerve to the ulnar intrinsic hand muscles using motor unit number estimation, a non-invasive electrophysiological technique. The investigators will also evaluate whether there is an associated improvement in hand function following the procedure.

Experimental protocol Subjects For this study, the investigators aim to recruit a prospective series of 60 patients with severe cubital tunnel syndrome causing marked motor axonal loss.

Primary outcome measures Motor unit number estimations of native axons in the ulnar nerve innervation the intrinsic hand muscles compared to those from the AIN.

Secondary outcomes

Motor function:

  1. Pinch strength using a pinch gauge ii) Grip strength using a Jamar dynamometer iii) Disabilities of Arm, Hand and Shoulder (DASH) Questionnaire

Procedures and follow up All outcomes will be measured at baseline and repeated at 3 and 6 months post op. Motor unit number estimation will be done using the multiple point stimulation technique. To briefly summarize, recording surface electrodes will be placed over the belly of the hypothenar muscles. To estimate the number of native ulnar axons innverating the hypothenar hand muscles, supramaximal stimulation of the ulnar nerve in the mid forearm above the site of AIN coaptation will be done. A sample of single motor unit action potentials will be obtained by discretely stimulating individual motor axons using finely graded stimuli. A motor unit number estimation will be calculated from the ratio of the compound muscle action potential amplitude and the average single motor unit action potentials. To estimate the motor unit innervation from the AIN, the same procedure will be done by stimulating the median nerve while recording from the hypothenar muscles.

Surgery Eligible patients will undergo surgical decompression of the ulnar nerve at the elbow. Additionally, a reverse end-to-side transfer to the ulnar nerve will be done using a terminal branch of the AIN to the pronator quadratus muscle. It will be coapted to the side of the motor fascicle of the ulnar nerve just above the wrist through a 5 mm epineurial window.

Statistical analysis To address the central question of AIN innervation, descriptive statistics (mean and sd) will be used to quantify the extent of nerve growth through the epineurial window created by the RETS procedure. Since there is no AIN innervation of the hypothenar muscles at baseline, growth of motor axons through the epineurial window should be easy to discern through motor unit number estimation. Changes in motor hand strength and disability following surgery will be compared using repaired measure one way ANOVA with time as the independent factor. With this being a pilot exploratory study, further analytic statistical analysis would not be justified as the sample size will be too small to allow for any meaningful interpretation.

Expected outcomes and significance This will be further aided by the very substantial distance difference between the entry point of the AIN to the ulnar nerve trunk at just above the wrist and the native ulnar motor axons that regenerate from the elbow. At less than 100 mm from the target muscles, many AIN motor axons should reach the hypothenar muscles by 3 months and all by 6 months. In contrast, the regenerating native ulnar motor axons would likely not reach the hand muscles for a year or more, as shown in the investigators' previous publications.

Given the importance of this critical question and the potential utilities of distal nerve transfers, this should be a worthwhile effort.

Being tested
nerve transfer
Keywords
nerve transfer, cubital tunnel syndrome, nerve generation
Medical subject headings
Cubital Tunnel Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nerve transferProcedure or surgery

    the anterior interosseous nerve will be used as a donor to reinnervation the injured ulnar nerve.

Study groups in NCT05242302
Study groupRoleWhat they receive
reverse end to side nerve transferExperimentalNot described
Receives: Procedure: nerve transfer
end to end nerve transferActive comparatorNot described
Receives: Procedure: nerve transfer
nerve decompressionActive comparatorNot described
Receives: Procedure: nerve transfer

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Motor nerve conduction study

    Amplitudes of the maximum compound muscle action potentials evoked by median nerve stimulation

    Measured: patients will be followed for 6 months after surgery

Secondary outcomes (1)
  1. Key pinch strength

    Dynamometer for isometric force quantification of pinch strength between the 1st and 2nd digits

    Measured: patients will be followed for 6 months after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2022
  2. Study start1 Jan 2019
  3. Primary completion31 Dec 2022
  4. Study completion28 Feb 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05242302
Sponsor's protocol ID
Pro00066610
Status last verified
Feb 2022
First submitted
31 Jan 2022
Last updated
6 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing nerve transfer in people with Nerve Injury and Surgery, run by University of Alberta at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Motor nerve conduction study (time frame: patients will be followed for 6 months after surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2023.

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