Enhancement of Functional Recovery After Peripheral Nerve Injury With Tacrolimus

NCT00950391 | Withdrawn Phase 1 DMC

• 1 other identifier: FK50600
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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:

1. 1.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;
2. 2.Correlate the quality of life outcome with assessment of functional recovery after surgical reconstruction of patients with severe peripheral nerve injuries of the extremities.

Conditions

Peripheral Nerve Injury

Keywords

peripheral nerve injury; peripheral nerve surgery; nerve repair; nerve graft

Outcome Measures

Primary Outcomes (2)

• Functional Recovery

  1-1.5 years

• Incidence of adverse events.

  1 year

Secondary Outcomes (2)

• Recovery time.

  1.5 years

• Recovery of sensation.

  1 year

Study Arms (1)

Tacrolimus

EXPERIMENTAL

Treatment with tacrolimus following nerve repair/reconstruction

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

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

Also known as: FK506, Prograf

Tacrolimus

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Washington University School of Medicine: lead

MeSH Terms

Conditions

Peripheral Nerve Injuries

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Thomas H Tung, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2009
• First Posted: July 31, 2009
• Study Start: August 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2015
• Last Updated: February 13, 2018

Record last verified: 2018-02