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

NCT00661453 | Completed Phase 1 Results DMC

• 2 other identifiers: 25409IND 79276
• Study Type: interventional
• Target: 40
• Locations: 3 countries
• Sites: 8

Brief 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.

Conditions

Spinal Muscular Atrophy Type I

Keywords

Spinal Muscular Atrophy; SMA; Valproic Acid

Outcome Measures

Primary Outcomes (2)

• Laboratory Safety Data

  -2 weeks, + 2 weeks, 3 months, 6 months

• 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)

  -2 weeks, time 0, 3 months, 6 months

Secondary Outcomes (6)

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

  monthly

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

  time 0, and monthly for 12 months

• Functional Motor Assessments: TIMPSI Scores

  -2 weeks, time 0, 3 months, 6 months

• Quantitative SMN mRNA and Protein Measures

  -2 weeks, time 0 , 3 months, or 6 months

• Maximum Ulnar CMAP Amplitude/Area and MUNE

  -2 weeks, time 0, 3 months, 6 months

Study Arms (1)

1

EXPERIMENTAL

All patients will receive VPA and carnitine.

Drug: Valproic Acid and Levocarnitine

Interventions

Valproic Acid and Levocarnitine DRUG

Drug: Valproic Acid and Levocarnitine; syrup; dosage is by weight

1

Eligibility Criteria

• Age: 2 Weeks - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead
• Families of Spinal Muscular Atrophy: collaborator
• Leadiant Biosciences, Inc.: collaborator

Study Sites (8)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Medical Center, Dept. of Neurology

Columbus, Ohio, 43210, United States

Location

University of Utah/Primary Children's Medical Center

Salt Lake City, Utah, 84132, United States

Location

University of Wisconsin Children's Hospital

Madison, Wisconsin, 53792-9988, United States

Location

Hospital Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Klinikum der Universität zu Köln

Cologne, 50924, Germany

Location

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MeSH Terms

Conditions

Spinal Muscular Atrophies of Childhood; Muscular Atrophy, Spinal

Interventions

Valproic Acid; Carnitine

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines

Results Point of Contact

• Title: Dr. Kathryn Swoboda
• Organization: University of Utah

swoboda@genetics.utah.edu

801-585-9717

Study Officials

• Kathryn Swoboda, M.D.

  University of Utah

  PRINCIPAL INVESTIGATOR

• Sandra P Reyna, M.D.

  Families of Spinal Muscular Atrophy

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Neurology and Pediatrics Director, Pediatric Motor Disorders Research Program

Study Record Dates

• First Submitted: April 14, 2008
• First Posted: April 18, 2008
• Study Start: April 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2012
• Last Updated: June 15, 2015
• Results First Posted: June 15, 2015

Record last verified: 2015-06

Locations

US (6); CA (1); DE (1)