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CARNIVAL Type I: Valproic Acid and Carnitine in Infants With Spinal Muscular Atrophy (SMA) Type I

Information source: University of Utah
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Spinal Muscular Atrophy Type I

Intervention: Valproic Acid and Levocarnitine (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: University of Utah

Official(s) and/or principal investigator(s):
Kathryn Swoboda, M.D., Principal Investigator, Affiliation: University of Utah
Sandra P Reyna, M.D., Study Director, Affiliation: Families of Spinal Muscular Atrophy

Summary

This is a multi-center trial to test safety and evaluate early treatment intervention with valproic acid and carnitine in moderating SMA symptoms of Type I infants.

Clinical Details

Official title: Phase I/II Trial of Valproic Acid and Carnitine in Infants With Spinal Muscular Atrophy Type I (CARNI-VAL Type I)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Laboratory Safety Data

Anthropometric Measures of Nutritional Status (Body Mass Index [BMI] Z-scores, Weight for Length Ratios, Lean/Fat Mass Via DEXA, Growth Parameters, and Triceps Skinfold Measures)

Secondary outcome:

Time to Death or Ventilator Dependence (Defined as >16 Hours/Day)

Primary Caregiver Functional Rating Scale for SMA Type I Subjects (PCFRS)

Functional Motor Assessments: TIMPSI Scores

Quantitative SMN mRNA and Protein Measures

Maximum Ulnar CMAP Amplitude/Area and MUNE

Whole Body DEXA Scanning for Lean Body Mass and Total Bone Mineral Density/ Content

Detailed description: Spinal muscular atrophy (SMA) is a genetic disorder that results in severe muscle weakness. It is one of the most common conditions causing muscle weakness in children. Patients with SMA most often develop weakness as babies or young children. Most people with SMA gradually lose muscle strength and abilities over time. Babies with the severe infantile form of SMA, SMA type I, usually lose abilities and strength quickly over a few weeks or months. Valproic acid (VPA) is a medicine that has been used for many years to treat patients with epilepsy. Recent research suggests that VPA may be able to upregulate expression of a backup copy of the SMN gene in SMA patient cell lines. In addition, some preliminary data suggests it may prolong survival in animal models of SMA. Because VPA can deplete carnitine in children with SMA Type I, carnitine is added to help prevent possible toxicity. In this multi-center trial, we will evaluate the effects of VPA/carnitine on infants with SMA type I. A variety of outcome measures, including assessment of safety, will be performed at each study visit to follow the course of the disease. The protocol includes two baseline visits over a period of two weeks, two clinical assessments on medication at 3 and 6 months, and then 6 months additional followup via telephone. Total duration of the study will be approximately 12 months.

Eligibility

Minimum age: N/A. Maximum age: 12 Months. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Laboratory documentation of SMN mutation/deletion consistent with a genetic

diagnosis of SMA

- Clinical diagnosis of SMA type I

- Age 2 weeks to 12 months

- Written informed consent of parents/guardian

Exclusion Criteria:

- Any clinical or laboratory evidence of hepatic or pancreatic insufficiency.

- Laboratory results drawn within 14 days prior to start of study drug demonstrating:

Liver transaminases (AST, ALT), lipase, amylase: > 1. 5 x ULN White Blood Cell Count: < 3 Neutropenia: <1 Platelet: <100K Hematocrit: <30, persisting over a 30-day period

- Serious illness requiring systemic treatment and/or hospitalization within two weeks

prior to study entry.

- Use of medications or supplements within 30 days of study enrollment that interfere

with VPA or carnitine metabolism; that increase the potential risks of VPA or carnitine; or that are hypothesized to have a beneficial effect in SMA animal models or human neuromuscular disorders, including riluzole, valproic acid, hydroxyurea, oral use of albuterol, sodium phenylbutyrate, butyrate derivatives, creatinine, growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, or agents anticipated to increase or decrease muscle strength or agents with presumed histone deacetylase (HDAC) inhibition.

- Infants who have participated in a treatment trial for SMA within 30 days of study

entry or who will become enrollees in any other treatment trial during the course of this study.

- Unwillingness to travel for study assessments.

- Coexisting medical conditions that contradict use of VPA/carnitine or travel to and

from study site.

Locations and Contacts

Klinikum der Universität zu Köln, Cologne 50924, Germany

Johns Hopkins University, Baltimore, Maryland 21287, United States

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

Ohio State University Medical Center, Dept. of Neurology, Columbus, Ohio 43210, United States

Hospital Sainte-Justine, Montreal, Quebec H3T 1C5, Canada

University of Utah/Primary Children's Medical Center, Salt Lake City, Utah 84132, United States

University of Wisconsin Children's Hospital, Madison, Wisconsin 53792-9988, United States

Additional Information

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Starting date: April 2008
Last updated: June 1, 2015

Page last updated: August 23, 2015

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