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.
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.
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:
- 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.
- Conditions
- Nerve Injury, Surgery
- 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 group | Role | What they receive |
|---|---|---|
| reverse end to side nerve transfer | Experimental | Not described Receives: Procedure: nerve transfer |
| end to end nerve transfer | Active comparator | Not described Receives: Procedure: nerve transfer |
| nerve decompression | Active comparator | Not described Receives: Procedure: nerve transfer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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.
- First posted16 Feb 2022
- Study start1 Jan 2019
- Primary completion31 Dec 2022
- Study completion28 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nerve InjuryStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
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
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of End-to-Side Nerve Transfer for Patients With Severe Cubital Tunnel Syndrome
- ClinicalTrials.gov ID
- NCT05242302
- Acronym / sponsor ID
- Pro00066610
- Conditions
- Nerve Injury, Surgery
- Keywords
- nerve transfer, cubital tunnel syndrome, nerve generation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 16 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| reverse end to side nerve transfer | Experimental | Procedure: nerve transfer |
| end to end nerve transfer | Active comparator | Procedure: nerve transfer |
| nerve decompression | Active comparator | Procedure: nerve transfer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nerve transferthe anterior interosseous nerve will be used as a donor to reinnervation the injured ulnar nerve. | Procedure or surgery | end to end nerve transfer, nerve decompression, reverse end to side nerve transfer |
Primary outcome
Motor nerve conduction study
Time frame: patients will be followed for 6 months after surgery
Amplitudes of the maximum compound muscle action potentials evoked by median nerve stimulation
1 secondary outcome
Key pinch strength
Time frame: patients will be followed for 6 months after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
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.