A Pilot Therapeutic Trial Using Hydroxyurea in Type I Spinal Muscular Atrophy Patients

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00568698
• Collaborator: (none)
• Enrollment: 29
• Location: 1
• Arms: 2
• Duration (Months): 97
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The objectives of this trial are: to establish a safety profile for use of Hydroxyurea in children with Type I Spinal Muscular Atrophy; to identify reliable outcome measures for HU treatment in Type I SMA; and to detect the clinical efficacy of HU treatment in children with Type I SMA.

Condition or Disease	Intervention/Treatment	Phase
Muscular Atrophy, Spinal	Drug: Hydroxyurea; Drug: Placebo to match hydroxyurea	Phase 1/Phase 2

Detailed Description

SMA is a neuromuscular disorder characterized by degeneration of spinal cord motor neurons and muscular atrophy. SMA is classified into three clinical subtypes according to the severity and age of onset (Types I, II and III). Type I SMA (also called severe, infantile or acute SMA, or Werdnig-Hoffman disease) is the most severe phenotype. The onset of symptoms is within the first 6 months of life, and weakness of intercostal muscles and lack of airway protection lead to respiratory insufficiency and aspiration pneumonia, often resulting in early infant death.

In our laboratory, our preliminary results indicate that HU treatment significantly increases both SMN mRNA expression and intact SMN protein levels in vitro. These data confirm previous observations that in vitro treatments of SMA lymphocytes with hydroxyurea resulted in augmentation of the SMN2 gene expression in a dose and time related manner. Based on these exciting pre-clinical data, coupled with the well-documented side-effect profile of HU in children, we are conducting a pilot clinical trial using HU in children with Type I SMA. This clinical trial study is intended to establish the safety profile in children with Type I SMA; to identify reliable outcome measures; and to detect the possible clinical efficacy of HU treatment in children with Type I SMA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Pilot Therapeutic Trial Using Hydroxyurea in Type I Spinal Muscular Atrophy Patients
• Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hydroxyurea	Drug: Hydroxyurea
Placebo Comparator: Placebo	Drug: Placebo to match hydroxyurea

Outcome Measures

Primary Outcome Measures

1. Safety: Frequency of Adverse Events/Lab Abnormalities [Up to 8 years, 1 month]

2. Efficacy: Length of Survival (LOS) and Age of Ventilator Dependence (AVD) [Up to 8 years, 1 month]

Secondary Outcome Measures

1. Motor Unit Number Estimation (MUNE) [Up to 8 years, 1 month]

2. Biomarker Assays: SMN Protein and SMN mRNA [Up to 8 years, 1 month]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 2 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:1. Laboratory confirmation of a homozygous deletion or mutation of the SMN1 gene 2. Clinical Diagnosis of Type I SMA (never achieved independent sitting) 3. Onset of disease before the age of 6 months 4. Enrollment in study within 6 months of diagnosis Exclusion Criteria:1. Known hematological disorders, such as chronic anemia (defined as platelet count less than 100,000/mm^3) in two contiguous measures in two weeks 2. Severe systemic disorders such as congenital heart disease, other major birth defects involving internal organs, or severe birth asphyxia 3. Participation in SMA clinical trials for other experimental drugs 4. Requiring continuous respiratory support before the initiation of HU treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Dr Ching H. Wang, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT00568698
• Other Study ID Numbers: SU-11012007-783; 78811; NCT00083746
• First Posted: Dec 6, 2007
• Last Update Posted: Oct 2, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Muscular Atrophy; Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood; Atrophy; Hydroxyurea

Study Results

Participant Flow

Pre-assignment Detail	Data are presented for all participants because data relating to arm assignment are no longer accessible; the Principal Investigator (PI) has left institution and all efforts to locate the data have been exhausted.

Arm/Group Title	All Participants
Arm/Group Description	Participants received hydroxyurea, or placebo to match hydroxyurea.
Period Title: Overall Study
STARTED	29
COMPLETED	18
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants received hydroxyurea, or placebo to match hydroxyurea.
Overall Participants	29
Age (Count of Participants)
<=18 years	29 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	13 44.8%
Male	16 55.2%

Outcome Measures

1. Primary Outcome

Title	Safety: Frequency of Adverse Events/Lab Abnormalities
Time Frame	Up to 8 years, 1 month

Outcome Measure Data

Analysis Population Description

Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.

Arm/Group Title	Hydroxyurea	Placebo
Arm/Group Description	Hydroxyurea	Placebo to match hydroxyurea
Measure Participants	0	0

2. Primary Outcome

Title	Efficacy: Length of Survival (LOS) and Age of Ventilator Dependence (AVD)
Time Frame	Up to 8 years, 1 month

Outcome Measure Data

Analysis Population Description

Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.

Arm/Group Title	Hydroxyurea	Placebo
Arm/Group Description	Hydroxyurea	Placebo to match hydroxyurea
Measure Participants	0	0

3. Secondary Outcome

Title	Motor Unit Number Estimation (MUNE)
Time Frame	Up to 8 years, 1 month

Outcome Measure Data

Analysis Population Description

Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.

Arm/Group Title	Hydroxyurea	Placebo
Arm/Group Description	Hydroxyurea	Placebo to match hydroxyurea
Measure Participants	0	0

4. Secondary Outcome

Title	Biomarker Assays: SMN Protein and SMN mRNA
Time Frame	Up to 8 years, 1 month

Outcome Measure Data

Analysis Population Description

Data for this outcome measure are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.

Arm/Group Title	Hydroxyurea	Placebo
Arm/Group Description	Hydroxyurea	Placebo to match hydroxyurea
Measure Participants	0	0

Adverse Events

Time Frame	Up to 8 years, 1 month
Adverse Event Reporting Description	Adverse events data are no longer accessible; the PI has left institution and all efforts to locate the data have been exhausted.
Arm/Group Title	Hydroxyurea		Placebo
Arm/Group Description	Hydroxyurea		Placebo to match hydroxyurea
All Cause Mortality
	Hydroxyurea		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Hydroxyurea		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Hydroxyurea		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.