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

Spinal Muscular Atrophy Type I Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00661453
• Other study ID #: 25409
• Secondary ID: IND 79276
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 14, 2008
• Last updated: June 1, 2015
• Start date: April 2008
• Est. completion date: June 2012

Study information

• Verified date: June 2015
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 12 Months

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy Type I

Intervention

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

Locations

Country	Name	City	State
Canada	Hospital Sainte-Justine	Montreal	Quebec
Germany	Klinikum der Universität zu Köln	Cologne
United States	Johns Hopkins University	Baltimore	Maryland
United States	Ohio State University Medical Center, Dept. of Neurology	Columbus	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Wisconsin Children's Hospital	Madison	Wisconsin
United States	University of Utah/Primary Children's Medical Center	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
University of Utah	Families of Spinal Muscular Atrophy, Sigma Tau Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

References & Publications (42)

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* Note: There are 42 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Laboratory Safety Data		-2 weeks, + 2 weeks, 3 months, 6 months	Yes
Primary	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	Yes
Secondary	Time to Death or Ventilator Dependence (Defined as >16 Hours/Day)		monthly	Yes
Secondary	Primary Caregiver Functional Rating Scale for SMA Type I Subjects (PCFRS)		time 0, and monthly for 12 months	No
Secondary	Functional Motor Assessments: TIMPSI Scores		-2 weeks, time 0, 3 months, 6 months	No
Secondary	Quantitative SMN mRNA and Protein Measures		-2 weeks, time 0 , 3 months, or 6 months	No
Secondary	Maximum Ulnar CMAP Amplitude/Area and MUNE		-2 weeks, time 0, 3 months, 6 months	No
Secondary	Whole Body DEXA Scanning for Lean Body Mass and Total Bone Mineral Density/ Content		-2 weeks or time 0, 3 months, 6 months	Yes