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Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANTSMA)

Primary Purpose

Spinal Muscular Atrophy

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Valproic Acid (VPA)

Placebo

About this trial

This is an interventional treatment trial for Spinal Muscular Atrophy focused on measuring Spinal Muscular Atrophy, Adult

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ambulatory adults with SMA 3 ages 18-60. The diagnosis of SMA must be documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder. Patients must be able to walk thirty feet without assistance (i.e. no canes, walkers).
Interest in participating and the ability to meet the study requirements.
Women of child bearing age are required to be on birth control or abstain while participating in the study.

Exclusion Criteria:

Non-ambulatory type 3 adults and all type 2 adults.
Patients with co-morbid conditions that preclude travel, testing or study medications.
Patients who have participated in a treatment trial for SMA in the 3 months prior to this trial, or plan on enrolling in any other treatment trial during the duration of this trial.
Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing.
Patients with a need for non-invasive ventilatory support (e.g. BiPAP) for > 12 hours/day
Transaminases, amylase or lipase > 3.0 x normal values, WBC < 3.0 or neutropenia < 1.0, platelet count < 100 K, or hematocrit < 30 persisting over a 30 day period
Use of medications or supplements which interfere with VPA metabolism and increase the potential risks of the medications, or are hypothesized to have a beneficial effect in SMA animal models or human neuromuscular disorders within 3 months of study enrollment. These agents include riluzole, creatine, butyrate derivatives, growth hormone, anabolic steroids, daily albuterol use, anticonvulsants, or other HDAC inhibitors.
Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding.

Sites / Locations

Ohio State University Medical Center, Dept. of Neurology

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Arm Description

For six months, half of patients are randomized into placebo . After 6 months, all patients are on treatment.

Cohort 1b patients are randomized onto treatment. After 6 months, all patients are on drug.

Outcomes

Primary Outcome Measures

The primary outcome for the study is change in muscle strength from baseline to six months in muscle strength as assessed by MVICT using a fixed testing system.

Secondary Outcome Measures

Change in SMAFRS

Change in strength assessed by hand-held dynamometer

Change in MUNE and CMAP

SMN2 copy number

Change in PFTs, including forced vital capacity (FVC) and negative inspiratory force (NIF)

Change in lean body mass through DEXA scanning

Change in distance walked in 6 minutes

Change in time to climb four standard stairs

Change in health-related QOL assessed through the modified sickness impact profile (SIP)

Full Information

NCT ID

NCT00481013

First Posted

May 30, 2007

Last Updated

December 5, 2016

Sponsor

University of Utah

Collaborators

Families of Spinal Muscular Atrophy, Abbott

1. Study Identification

Unique Protocol Identification Number

NCT00481013

Brief Title

Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy

Acronym

VALIANTSMA

Official Title

Prospective Controlled Trial of Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy (VALIANTSMA) Study

Study Type

Interventional

2. Study Status

Record Verification Date

December 2016

Overall Recruitment Status

Completed

Study Start Date

July 2007 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Utah

Collaborators

Families of Spinal Muscular Atrophy, Abbott

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objective of this proposal is to determine whether oral VPA is effective in treating SMA in adult patients.

Detailed Description

Participation in this study entails six visits and seven to eight blood draws over 13 months. Each visit entails a stay of two days and one night at the General Clinical Research Center (GCRC). Subjects who live within driving distance will be allowed to participate in the study without an overnight stay through two consecutive outpatient visits. All subjects will be evaluated at two screening visits 2-4 weeks apart to determine eligibility for participation. Eligible subjects will be randomized to receive VPA or placebo for the first six months. At the six-month visit, patients will be evaluated and crossed over to the other regimen.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Muscular Atrophy

Keywords

Spinal Muscular Atrophy, Adult

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Placebo Comparator

Arm Description

For six months, half of patients are randomized into placebo . After 6 months, all patients are on treatment.

Arm Title

Arm Type

Active Comparator

Arm Description

Cohort 1b patients are randomized onto treatment. After 6 months, all patients are on drug.

Intervention Type

Drug

Intervention Name(s)

Valproic Acid (VPA)

Other Intervention Name(s)

Depakote, Carnitor

Intervention Description

Drug: Valproic Acid and Levocarnitine; capsules

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

For six months, pts are randomized into placebo or treatment. After 6 months, all pts are on treatment

Primary Outcome Measure Information:

Title

The primary outcome for the study is change in muscle strength from baseline to six months in muscle strength as assessed by MVICT using a fixed testing system.

Time Frame

13 months

Secondary Outcome Measure Information:

Title

Change in SMAFRS

Time Frame

13 months

Title

Change in strength assessed by hand-held dynamometer

Time Frame

13 months

Title

Change in MUNE and CMAP

Time Frame

13 months

Title

SMN2 copy number

Time Frame

13 months

Title

Change in PFTs, including forced vital capacity (FVC) and negative inspiratory force (NIF)

Time Frame

13 months

Title

Change in lean body mass through DEXA scanning

Time Frame

13 months

Title

Change in distance walked in 6 minutes

Time Frame

13 months

Title

Change in time to climb four standard stairs

Time Frame

13 months

Title

Change in health-related QOL assessed through the modified sickness impact profile (SIP)

Time Frame

13 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ambulatory adults with SMA 3 ages 18-60. The diagnosis of SMA must be documented by the homozygous deletion of both SMN1 genes on standard genetic tests for the disorder. Patients must be able to walk thirty feet without assistance (i.e. no canes, walkers). Interest in participating and the ability to meet the study requirements. Women of child bearing age are required to be on birth control or abstain while participating in the study. Exclusion Criteria: Non-ambulatory type 3 adults and all type 2 adults. Patients with co-morbid conditions that preclude travel, testing or study medications. Patients who have participated in a treatment trial for SMA in the 3 months prior to this trial, or plan on enrolling in any other treatment trial during the duration of this trial. Patients who are, in the investigator's opinion, mentally or legally incapacitated from providing informed consent for the study, or are otherwise unable to meet study requirements or cooperate reliably with study procedures, especially strength testing. Patients with a need for non-invasive ventilatory support (e.g. BiPAP) for > 12 hours/day Transaminases, amylase or lipase > 3.0 x normal values, WBC < 3.0 or neutropenia < 1.0, platelet count < 100 K, or hematocrit < 30 persisting over a 30 day period Use of medications or supplements which interfere with VPA metabolism and increase the potential risks of the medications, or are hypothesized to have a beneficial effect in SMA animal models or human neuromuscular disorders within 3 months of study enrollment. These agents include riluzole, creatine, butyrate derivatives, growth hormone, anabolic steroids, daily albuterol use, anticonvulsants, or other HDAC inhibitors. Women who are pregnant or who intend to become pregnant while participating in the research study or who are breastfeeding.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John T Kissel

Organizational Affiliation

Ohio State University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Sandra P Reyna, M.D.

Organizational Affiliation

Families of Spinal Muscular Atrophy

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Kathryn J Swoboda, M.D.

Organizational Affiliation

University of Utah

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ohio State University Medical Center, Dept. of Neurology

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

12. IPD Sharing Statement

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Valproic Acid in Ambulant Adults With Spinal Muscular Atrophy

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