Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05242302 |
| Other study ID # |
Pro00066610 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2019 |
| Est. completion date |
February 28, 2023 |
Study information
| Verified date |
February 2022 |
| Source |
University of Alberta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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. 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.
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:
i) 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.
