An Open-label Study of the Effects of Acetyl-L-Carnitine on Cardiovascular Outcomes in Friedreich's Ataxia

The purpose of this study is to learn how treatment with acetyl-L-carnitine (ALCAR) will affect the hearts of patients with Friedreich's Ataxia as well as how it may affect other symptoms of Friedreich's Ataxia such as difficulties with balance, walking, or upper arm function.

Study Overview

• Status: Unknown
• Conditions: Friedreich's Ataxia
• Intervention / Treatment: Drug: Acetyl-L-Carnitine

Detailed Description

This study is an open label, pilot study of ALCAR in subjects with FA. In this study 20 patients with FA will receive ALCAR every day for 24 months. At the study endpoint, subjects will be assessed for changes in cardiovascular outcomes and FA symptoms. To determine the effects of LC on changes in cardiomyopathy, echocardiography with strain rate will be calculated. This technique has been validated in clinical studies and used in other studies of FA patients for the comparison of regional deformation and myocardial wall thickness.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • University of South Florida
      • Contact: Jessica Shaw, MPH; Phone Number: 813-974-5909; Email: jshaw@health.usf.edu
      • Contact: Tanya Aranca, B.S.; Phone Number: 813-974-5909; Email: taranca@health.usf.edu
      • Principal Investigator: Theresa Zesiewicz, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatients with Friedreich's Ataxia diagnosed by a movement disorder specialist and confirmed by genetic testing (of the patient or in a first degree relative of the patient). Subject may be non-ambulatory.
2. Age 18 years to 80 years.
3. Stable medical condition for 3 months prior to screening.
4. Women of child-bearing potential must use a reliable method of contraception and must provide a negative pregnancy test at entry into the study.
5. If on cardiac medications such as beta-blockers or ace inhibitors, patients must be on a stable dose for 6 months prior to study entry and for the duration of the study.
6. Friedreich's Ataxia patients with systolic or diastolic dysfunction present on echocardiogram and ejection fraction between 35% - 65% at screening.
7. Subjects with ejection fractions < 50% need to be stable and on optimal heart failure therapy for at least 2 weeks prior to screening.

Exclusion Criteria:

1. Any unstable illness or concomitant medical condition that, in the investigator's opinion, precludes participation in this study. This includes other disorders that may affect gait or balance (stroke, arthritis, etc).
2. Pregnancy or lactation.
3. Concurrent participation in another clinical study where use of an investigational product is used. Subjects who are currently enrolled in the Friedreich's Ataxia Clinical Outcome Measures Study at any site will be allowed to enroll in this study as well.
4. Any use of the investigational product within the past 30 days.
5. Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini Mental Status Exam score less than 25).
6. Legal incapacity or limited legal capacity.
7. History of stroke.
8. Subjects with a history of thyroid disease (hypothyroidism). Clinical laboratory evaluations of thyroid stimulating hormone levels taken 3 months prior to the study or at screening will be used to confirm absence of current thyroid problems.
9. Subjects with a history of seizures.
10. Subjects taking warfarin or acenocoumarol.
11. Presence of severe renal disease (estimated creatinine clearance <50 mL/min) or hepatic disease (AST or Alanine transaminase(ALT)>2x times normal) (as evidenced by labs reported within the past 6 months).
12. Clinically significantly abnormal white blood cell, hemoglobin or platelet count (as evidenced by labs reported within the past 6 months).

13. Subjects with blood work showing carnitine deficiency (<60nmol/mg total carnitine in the urine or <35umol/L total carnitine in the plasma).

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acetyl-L-Carnitine; Open-label administration of Acetyl-L-Carnitine, up to 2 g/day for 24 months.	Drug: Acetyl-L-Carnitine; Acetyl-L-Carnitine, 2 g/day, up to 24 months.; Other Names: ALCAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To observe the changes in cardiac functioning in patients with Friedreich's Ataxia between study endpoint and baseline.	Every 12 months, up to 24 months
To assess the changes in Friedreich's Ataxia symptoms and severity (as measured by clinical rating scales) compared to baseline.	Every 6 months, up to 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in patient global impression of improvement	Every 6 months, up to 24 months
Changes in Time 25-foot Walk	Every 6 months, up to 24 months
Changes in frequency and severity of adverse events	Every 6 months, up to 24 months
Changes in patient quality of life (SF-36)	Every 6 months, up to 24 months
Changes in clinical global impression of improvement	Every 6 months, up to 24 months

Collaborators and Investigators

• Sponsor: University of South Florida

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: July 3, 2013
• First Submitted That Met QC Criteria: August 9, 2013
• First Posted (Estimate): August 13, 2013

Study Record Updates

• Last Update Posted (Estimate): April 12, 2016
• Last Update Submitted That Met QC Criteria: April 11, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Nootropic Agents; Acetylcarnitine
• Other Study ID Numbers: ALCAR-8499