A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00568802
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 2
• Actual Duration (Months): 74
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The objectives of this trial are: to establish a safety profile for use of Hydroxyurea in children with Types II and III Spinal Muscular Atrophy; to identify reliable outcome measures for HU treatment in Types II and III SMA; and to detect the clinical efficacy of HU treatment in children with Types II and III 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 II (intermediate) SMA has its onset in early childhood (prior to 18 months) and is characterized by the failure to stand or walk unassisted. Individuals with Type III SMA (mild SMA or Kugelberg-Welander disease) typically develop symptoms after 18 months of age and display a wide range of clinical heterogeneity. The clinical spectrum ranges from rapid progressive weakness resulting in wheelchair dependence in late childhood to patients being able to walk in adult years and living productive and independent lifestyles for the majority of their lives.

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 Types II and III SMA. This clinical trial study is intended to establish the safety profile in children with Types II and III SMA; to identify reliable outcome measures; and to detect the possible clinical efficacy of HU treatment in children with Types II and III SMA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Pilot Therapeutic Trial Using Hydroxyurea in Type II and Type III Spinal Muscular Atrophy Patients
• Actual Study Start Date: Jan 1, 2004
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Efficacy: Functional Motor Testing, Including Gross Motor Function Measure (GMFM) and Timed Motor Tests [Up to 6 years, 2 months]

2. Safety: Frequency of Adverse Events/Lab Abnormalities [Up to 6 years, 2 months]

Secondary Outcome Measures

1. Pulmonary Function Testing [Up to 6 years, 2 months]

2. Motor Unit Number Estimation (MUNE) [Up to 6 years, 2 months]

3. Biomarker Assays: SMN Protein and SMN mRNA [Up to 6 years, 2 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 10 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. (Type II) Can sit independently but cannot walk without support by the age of 16 months and never achieve independent walking thereafter; OR (Type III) Can walk independently within the first 2 years of life, but showing rapid progression of weakness resulting in the loss of independent ambulation by 6 years of age 3. Patient is older than 16 months and younger than 8 years old at the time of enrollment

Exclusion Criteria:1. Known hematological disorders, other systemic disorders, or severe birth asphyxia 2. Participation in SMA clinical trials for other experimental drugs 3. 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: NCT00568802
• Other Study ID Numbers: SU-11012007-781; 79233; NCT00084006
• 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	27
COMPLETED	24
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participants received hydroxyurea, or placebo to match hydroxyurea.
Overall Participants	27
Age (Count of Participants)
<=18 years	27 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	12 44.4%
Male	15 55.6%

Outcome Measures

1. Primary Outcome

Title	Efficacy: Functional Motor Testing, Including Gross Motor Function Measure (GMFM) and Timed Motor Tests
Time Frame	Up to 6 years, 2 months

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	Safety: Frequency of Adverse Events/Lab Abnormalities
Time Frame	Up to 6 years, 2 months

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	Pulmonary Function Testing
Time Frame	Up to 6 years, 2 months

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	Motor Unit Number Estimation (MUNE)
Time Frame	Up to 6 years, 2 months

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

5. Secondary Outcome

Title	Biomarker Assays: SMN Protein and SMN mRNA
Time Frame	Up to 6 years, 2 months

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 6 years, 2 months
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.