Enhancement of Functional Recovery After Peripheral Nerve Injury With Tacrolimus

Sponsor

Washington University School of Medicine (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00950391

Collaborator

(none)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

Brief Summary

Tacrolimus (FK506) is an immunosuppressive medication that promotes organ allograft survival. It has also been shown to enhance nerve regeneration and muscle reinnervation in animals but these properties have not previously been studied in patients. Moreover, currently there is no method in clinical use to speed the rate of recovery after nerve injury. The objective of this study is to explore the ability of tacrolimus to benefit the treatment of patients with peripheral nerve injury. To minimize the morbidity of tacrolimus therapy, its phase-specific effects on nerve regeneration and muscle reinnervation will be defined in the murine model to permit further limitation of the duration of therapy. The investigators hypothesize that treatment with tacrolimus after autogenous peripheral nerve reconstruction will accelerate nerve regeneration, reduce the period of denervation and improve muscle reinnervation and recovery in patients with peripheral nerve injury.

There are 2 specific aims:

Determine the safety and efficacy of tacrolimus following reconstructive nerve surgery in a double-blind placebo-controlled randomized pilot clinical trial of patients with severe nerve injuries of the extremities;
Correlate the quality of life outcome with assessment of functional recovery after surgical reconstruction of patients with severe peripheral nerve injuries of the extremities.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Nerve Injury	Drug: Tacrolimus	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Enhancement of Functional Recovery After Peripheral Nerve Injury With Tacrolimus

Study Start Date :

Aug 1, 2010

Anticipated Primary Completion Date :

Sep 1, 2014

Anticipated Study Completion Date :

Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tacrolimus Treatment with tacrolimus following nerve repair/reconstruction	Drug: Tacrolimus Tacrolimus 3 mg/day taken twice daily to maintain blood level of 3-6 ng/ml for duration of 1 year or less Other Names: FK506, Prograf

Arm

Intervention/Treatment

Experimental: Tacrolimus

Treatment with tacrolimus following nerve repair/reconstruction

Drug: Tacrolimus

Tacrolimus 3 mg/day taken twice daily to maintain blood level of 3-6 ng/ml for duration of 1 year or less

Other Names:

FK506, Prograf

Outcome Measures

Primary Outcome Measures

Functional Recovery [1-1.5 years]
Incidence of adverse events. [1 year]

Secondary Outcome Measures

Recovery time. [1.5 years]
Recovery of sensation. [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

have deficit of upper extremity function of MRC grade 0-2
are candidates for surgical reconstruction
are no more than 10 months after their injury
have no ongoing infectious or wound healing complications related to injury or previous surgery or otherwise
have no history of cancer or have been treated and free of cancer for at least 5 years
age 18-50
agree to participate in the study

Exclusion Criteria:

positive HIV or hepatitis blood test
recent history of cancer within the past 5 years
history of severe and recurrent infections (such as hidradenitis suppurativa)
presence of ongoing and unresolved infectious concerns related to original injury or previous surgery (such as osteomyelitis, wound infection) or otherwise
presence of ongoing wound healing problems related to the injury or previous surgery or otherwise
presence of moderate or severe liver disease as indicated by aspartate transaminase (AST), alanine transaminase (ALT), amino alkaline phosphatase, or total bilirubin levels greater than the upper limit of normal (ULN)
creatinine level ≥ 1.0 mg/dl or more than ULN
hemoglobin value of <9.0 mg/dl, a white blood cell count <3,000 cells/mm3, or platelet count <100,000 platelets/mm3
uncontrolled hypertension with systolic blood pressure >160 mm Hg and diastolic blood pressure >90 mm Hg at screening and baseline
hyperkalemia (serum K > ULN)
pancreatitis or diabetes mellitus (fasting blood sugar ≥ 110 mg/dl or postprandial blood sugar ≥ 160 mg/dl) or a history of these
heart disease or abnormal electrocardiogram (ECG) especially arrhythmia and change in ST/T or a previous history of these
history of serious drug hypersensitivity
age less than 18 or greater than 50
incarceration prior to or at the time of consideration for enrollment (any participant who becomes incarcerated during the course of the study will be excluded)