Clinical trial NCT02141035: Acetyl-l-carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome
Official title: Acetyl-l-carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome; a Randomized Control Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Carpal Tunnel Syndrome
Compression Neuropathy
Keywords: Acetyl-l-carnitine
Carpal tunnel syndrome
Motor unit number estimation
Compression neuropathy
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2014-05-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study Hypothesis: Acetyl-l-carnitine increases nerve regeneration in patients with severe carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is common, affecting almost 3% of the general population. In severe cases, nerve regeneration and functional recovery are incomplete even with surgery. The goal of this pilot project is to test a potentially promising medication, acetyl-l-carnitine (ALCAR). We will use a randomized, double blinded, placebo controlled study design. Along with surgery, those in the treatment group will also receive ALCAR while the other half in the control group will be given placebo. To gauge the effects of ALCAR, we will compare motor and sensory nerve growth as well as functional outcomes. The data from this study will provide crucial information when designing a full scale clinical trial. If successful, this will represent an important first step in finding a novel treatment to improve functional outcomes in patients with severe CTS.

Detailed description: Trial Conduct: This study will be conducted in compliance with the protocol approved by both the University of Alberta Health Research Ethics Board (HREB) and Health Canada. The study will be carried out according to Good Clinical Practice standards. No deviation from the protocol will occur once approved, unless the protocol has put patients at risk. If deviation needs to occur, both HREB and Health Canada will be notified. Written amendments will be submitted to both HREB and Health Canada for their approval.

Population Adult patients suffering from severe CTS would be a population of the interest. Severity of CTS is defined by clinical symptoms and electromyography (EMG) results. These patients will then be recruited for baseline studies, motor unit number estimation (MUNE). Motor unit number estimation is an EMG technique that quantifies the amount of motor units a muscle contains. In various forms of neuropathies, the MUNE decreases. For our study, patients will be included only if their MUNE is 2 standard deviations below normal. These patients will be identified from referrals to plastic surgery clinics or EMG clinics for management.Pre-study Screening and Baseline Evaluation The subject will have a complete physical exam including clinical labs and an ECG. Only those who have normal laboratory and ECG findings will be enrolled in the study.

Randomization Randomization - After enrollment, patients will be randomized to placebo or acetyl-l-carnitine. A statistician will be employed to develop a randomization sequence. Randomization will be kept on a computer under password encryption. The randomization sequence will only be broken if an adverse event occurs to a patient. At the end of the study the statistician will provide the research team with the randomization sequence codes.

Blinding - The study will be administered in a double-blind manner. The randomization sequence will be kept confidential and only accessible to authorized personnel. Pharmacy will distribute identical pills labelled in bottles with A or B. The research team will be unaware of which contains the study drug or placebo. This will be maintained until the final follow-up has occurred when the research team will be unblinded.

Duration The duration of the study is approximately 13 months for each patient. Screening and baseline evaluation will occur within 1 month preoperatively. The investigators will review and document the screening laboratory tests and ECG results. Acetyl-l-carnitine regimen will begin immediately following surgery. This will be continued for 2 months duration. The patient will then complete follow-up visits at 1, 2, 3, 6, and 12 month intervals. At some of those visits, safety monitoring will include periodic blood chemistries, vital signs and evaluation of overall clinical condition (details shown in table above). All clinically relevant changes occurring during the study will be examined and documented. In cases where laboratory abnormalities are detected, appropriate medical management and advice will be provided.

Eligibility criteria: Inclusion Criteria:

* Patients will be recruited from the University of Alberta Hospital referred for CTS. Inclusion criteria will include adult patients (over age 18) with at least one of the following symptoms:

  1. numbness and parenthesis in the median nerve distribution;
  2. Precipitation of those symptoms by repetitive motions that are relieved by rubbing and or shaking the hands;
  3. Nocturnal awakening by those sensory symptoms, or
  4. Weakness of thumb abduction and thenar atrophy.

Exclusion Criteria:

1. Motor unit loss in the median nerve less than 2 SD below the mean for the age as determined by nerve conduction studies.
2. The presence of other neurologic conditions
3. Previous carpal tunnel release surgery
4. Cognitive impairment that renders the patient unable to provide informed consent;
5. Pregnancy

Primary outcomes:
measure: Change in motor unit number estimates
timeFrame: Baseline, 3, 6, and 12 months
Secondary outcomes:
measure: Change in two point discrimination
timeFrame: Baseline, 3, 6, and 12 months
measure: Change in pressure sensitivity using Semmes-Weinstein Monofilaments
timeFrame: Baseline, 3, 6, and 12 months
measure: Change in cold detection threshold
timeFrame: Baseline, 3, 6, and 12 months
measure: Change in pain detection thresholds
timeFrame: Baseline, 3, 6, and 12 months
measure: Change in hand dexterity using the Purdue Pegboard
timeFrame: Baseline, 3, 6, and 12 months
measure: Change in disability scores using the Disability of Arm, Shoulder and Hand questionnaire
timeFrame: Baseline, 3, 6, and 12 months
measure: Change in hand symptoms using the Levine questionnaire for carpal tunnel syndrome
timeFrame: Baseline, 3, 6, and 12 months
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Glenrose Hosptial
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
Study officials:
affiliation: Professor, University of Alberta
name: Ming Chan, MB,ChB
role: PRINCIPAL_INVESTIGATOR
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