Harnessing Neuroplasticity to Enhance Functional Recovery During Chronic Recovery From Upper Extremity Nerve Repair

Sponsor

University of Missouri-Columbia (Other)

Overall Status

Completed

CT.gov ID

NCT03610763

Collaborator

Washington University School of Medicine (Other), Christine M. Kleinert Institute for Hand and Microsurgery (Other)

121

Enrollment

Locations

Arms

Actual Duration (Months)

40.3

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study adopts a strategy that has arisen from basic neuroscience research on facilitating adaptive brain plasticity and applies this to rehabilitation to improve functional recovery in peripheral nervous system injuries (including hand transplantation, hand replantation, and surgically repaired upper extremity nerve injuries). The technique involves combining behavioral training with transcranial direct current stimulation (tDCS)-a non-invasive form of brain stimulation capable of facilitating adaptive changes in brain organization.

Condition or Disease	Intervention/Treatment	Phase
Hand Transplantation Peripheral Nerve Injuries Neurologic Rehabilitation	Device: Transcranial Direct Current Stimulation Behavioral: Modified Constraint Induced Movement Therapy	N/A

Detailed Description

This study will implement and evaluate an innovative program of post hand transplant rehabilitation; one that harnesses recent discoveries in neuroscience to facilitate long-term, experience-dependent adaptations within the brain's sensory and motor systems. The current approach to rehabilitation of function in allogeneic hand transplant recipients is largely the same as standard-of-care following hand replantation (re-attachment) and peripheral nerve repairs. This involves an eclectic combination of traditional therapies. In seeking to improve on this approach, there is potentially much to be gained by considering evidence that limb amputation not only impacts the peripheral nervous system but also the brain, and tailoring interventions accordingly.

Study Design

Study Type:

Interventional

Actual Enrollment :

121 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Harnessing Neuroplasticity to Enhance Functional Recovery in Allogeneic Hand Transplant and Heterotopic Hand Replant Recipients

Actual Study Start Date :

Aug 15, 2018

Actual Primary Completion Date :

Sep 14, 2021

Actual Study Completion Date :

Sep 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Transplantation/Replantation Patients Can plateaued hand function in hand transplantation patients/hand replantation patients in the chronic stage of recovery be facilitated by use of bi-hemispheric transcranial direct current stimulation (tDCS) combined with modified Constraint Induced Movement Therapy (CIMT)?	Device: Transcranial Direct Current Stimulation Transcranial direct current stimulation (tDCS) is a portable neurostimulation method that modulates cortical excitability. The technique involves placing two saline-soaked electrodes (anode and cathode) on the scalp and passing a small direct current (1.5 milliamps; mA) between them. Cortex underlying the anode is more easily excited due to lowered thresholds for depolarization of glutamatergic neurons, while thresholds are increased in neurons beneath the cathode, making them less excitable. Sham stimulation is easily implemented, and the technique can be effectively double-blinded. Other Names: tDCS Behavioral: Modified Constraint Induced Movement Therapy In CIMT, patients are required to wear a mitt that restricts use of the unaffected limb while they practice structured tasks and also engage in activities of daily living. Other Names: CIMT
Active Comparator: Nerve Injury Patients active Can plateaued hand function in peripheral nervous system injuries in the chronic stage of recovery be facilitated by use of bi-hemispheric transcranial direct current stimulation (tDCS) combined with modified Constraint Induced Movement Therapy (CIMT)?	Device: Transcranial Direct Current Stimulation Transcranial direct current stimulation (tDCS) is a portable neurostimulation method that modulates cortical excitability. The technique involves placing two saline-soaked electrodes (anode and cathode) on the scalp and passing a small direct current (1.5 milliamps; mA) between them. Cortex underlying the anode is more easily excited due to lowered thresholds for depolarization of glutamatergic neurons, while thresholds are increased in neurons beneath the cathode, making them less excitable. Sham stimulation is easily implemented, and the technique can be effectively double-blinded. Other Names: tDCS Behavioral: Modified Constraint Induced Movement Therapy In CIMT, patients are required to wear a mitt that restricts use of the unaffected limb while they practice structured tasks and also engage in activities of daily living. Other Names: CIMT
No Intervention: Actigraphy Testing We will acquire a set of actigraphy data from a group of hand transplant/replant patients and unilateral, adult amputees in order to evaluate typical patterns of limb use prior to hand transplantation and to investigate prosthesis utilization.

Arm

Intervention/Treatment

Active Comparator: Transplantation/Replantation Patients

Can plateaued hand function in hand transplantation patients/hand replantation patients in the chronic stage of recovery be facilitated by use of bi-hemispheric transcranial direct current stimulation (tDCS) combined with modified Constraint Induced Movement Therapy (CIMT)?

Device: Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a portable neurostimulation method that modulates cortical excitability. The technique involves placing two saline-soaked electrodes (anode and cathode) on the scalp and passing a small direct current (1.5 milliamps; mA) between them. Cortex underlying the anode is more easily excited due to lowered thresholds for depolarization of glutamatergic neurons, while thresholds are increased in neurons beneath the cathode, making them less excitable. Sham stimulation is easily implemented, and the technique can be effectively double-blinded.

Other Names:

tDCS

Behavioral: Modified Constraint Induced Movement Therapy

In CIMT, patients are required to wear a mitt that restricts use of the unaffected limb while they practice structured tasks and also engage in activities of daily living.

Other Names:

CIMT

Active Comparator: Nerve Injury Patients active

Can plateaued hand function in peripheral nervous system injuries in the chronic stage of recovery be facilitated by use of bi-hemispheric transcranial direct current stimulation (tDCS) combined with modified Constraint Induced Movement Therapy (CIMT)?

Device: Transcranial Direct Current Stimulation

Other Names:

tDCS

Behavioral: Modified Constraint Induced Movement Therapy

In CIMT, patients are required to wear a mitt that restricts use of the unaffected limb while they practice structured tasks and also engage in activities of daily living.

Other Names:

CIMT

No Intervention: Actigraphy Testing

We will acquire a set of actigraphy data from a group of hand transplant/replant patients and unilateral, adult amputees in order to evaluate typical patterns of limb use prior to hand transplantation and to investigate prosthesis utilization.

Outcome Measures

Primary Outcome Measures

Change from Baseline Dellon Modified Moberg Pick-Up Test performance at two weeks. [Baseline, immediately after end of intervention (+/- 3 days).]
This functional test measures quality of sensibility of the hand. This outcome measure will investigate any change in participant performance between pre- and post-intervention sessions of the Dellon Modified Moberg Pick-Up Test.

Secondary Outcome Measures

Change from Baseline Action Research Arm Test (ARAT) performance at two weeks. [Baseline, immediately after end of intervention (+/- 3 days).]
The Action Research Arm Test (ARAT) measures limb function by having participants pick up various objects of different sizes, different weights, and different shapes (e.g., a glass of water, a cricket ball). This secondary outcome measure will investigate any change in participant performance between pre- and post-intervention sessions of the ARAT.
Change from baseline upper limb movement as measured by actigraphy-derived variables during everyday life at periodic intervals after intervention. [Baseline, post intervention at week 1, post intervention at 1 month, post intervention at 3 months, post intervention at 6 months.]
This secondary outcome measure will employ actigraphy on participants to measure limb movement in everyday life before and after the intervention. Participants will wear wrist-watch like devices that contain accelerometers on each upper extremity in 24-72 hour sessions. Two primary variables will quantify upper limb activity from accelerometer data: the Bilateral Magnitude and the Magnitude Ratio. The Bilateral Magnitude quantifies the intensity of activity across both limbs, whereas the Magnitude Ratio quantifies the contribution of each limb to activity. This outcome measure will investigate the change in the Bilateral Magnitude and Magnitude Ratio between a baseline pre-intervention test and post-intervention actigraphy sessions performed within one week of completion of the intervention, at 1 month post-intervention, 3-months post intervention, and 6-months post intervention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Individuals whom have received a unilateral allogeneic transplantation proximal to the wrist and are at the chronic stage of recovery (approx. 12 - 18 months following surgery, when Tinel's sign reaches the distal fingertips).
Individuals whom have undergone a complete amputation the hand between the wrist and elbow followed by successful re-attachment and are at the chronic stage of recovery (approx. 12 - 18 months following surgery, when Tinel's sign reaches the distal fingertips).
Individuals whom have undergone repairs of the median, ulnar, or other related or nearby nerve(s) following complex volar forearm lacerations or other injuries between the distal wrist crease and the flexor musculotendinous junctions. Individuals must be at the chronic stage of recovery (approx. 12 - 18 months following surgery, when Tinel's sign reaches the distal fingertips).

Exclusion Criteria:

Individuals with significant/severe brain trauma
Serious psychiatric conditions
Chronic or severe neurological conditions.
Current pregnancy
History of seizures or unexplained loss of consciousness
Metallic implants above the chest
Certain implanted medical devices.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Christine Kleinert Institute for Hand & Microsurgery	Louisville	Kentucky	United States	40202
2	University of Missouri	Columbia	Missouri	United States	65211
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110