Spinal Muscular AtrophyPhase 2/3NCT00485511
A Trial of Hydroxyurea in Spinal Muscular Atrophy
A Phase 2/3 study testing Hydroxyurea in people with Spinal Muscular Atrophy, run by Kaohsiung Medical University Chung-Ho Memorial Hospital at 1 site in Taiwan.
Trial summary
Spinal muscular atrophy (SMA) is an autosomal recessive disorder in humans which results in the loss of motor neurons. It is caused by reduced levels of the survival motor neuron (SMN) protein as a result of loss or mutation of the SMN1 gene. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- Hydroxyurea
- How many people
- Not given
- Where
- 1 siteTaiwan
- Study dates
- Jun 2007to Jun 2009
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- Child, Adult, Older adult
Who may be able to join
- Sixty SMA patients fulfilled the diagnostic criteria of SMA as defined by the International SMA Consortium (Munsat, 1992), and all had homozygous deletion of SMN1 gene but carried SMN2 gene (Chang, 1995; 1997)
- The subjects shall each have the age older than 4 years.
- The subjects (if age > 20 years old) or their parents (if subject age < 20 years old) shall agree with the trial and have signed the informed consents.
Who cannot join
- The subjects shall not have hematological diseases, other severe systemic diseases and congenital anomalies except for SMA.
- The subjects shall not have severe perinatal asphyxia history.
- The subjects shall not be with respiratory assists.
- The subjects shall have normal hepatic and renal functions in the pre-trial examination.
- The subjects shall not have received operation with generalized anesthesia in past half a year.
- The subjects shall not have acceded to other clinical trials in past half a year.
- The subjects shall not get in this trial if they could not complete the course.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial of Hydroxyurea in Spinal Muscular Atrophy
Spinal muscular atrophy (SMA) is an autosomal recessive disorder in humans which results in the loss of motor neurons. It is caused by reduced levels of the survival motor neuron (SMN) protein as a result of loss or mutation of the SMN1 gene. SMN protein is encoded by two genes, SMN1 and SMN2, which essentially differ by an single nucleotide in exon 7. As a result, the majority of the transcript from SMN2 lacks exon 7. According to clinical severity, SMA was classified to three types, including type I, type II, and type III.
Drugs capable of modifying the transcription pattern of SMN2 to increase the full-length of SMN mRNA expression and the amount of SMN protein may have therapeutic effects for SMA patients. In order to test this hypothesis, we used EBV-transformed lymphoblastoid cell lines derived from the different types of SMA patients to screen the effect of various drugs on SMN2 gene expression. Hydroxyurea (HU) was found to be effective among the drugs we tested. HU is an effective therapeutic agent for patients with thalassemia and sickle cell disease which the toxicity is minimal and is well-tolerated and safely used in children. We had undergone a small-scaled 33 SMA patients randomized pilot trial (HU treatment for 8 weeks and then follow up drug-free 8 weeks) to evaluate the effect of HU in SMA patients and we got a promising preliminary data. We found that HU could significantly increase in the manual muscle testing scores at 4 weeks, and full-length SMN mRNA level in the 30mg/kg/day subgroup at 8 weeks relative to baseline, and it is safe under the dose 30mg/kg/day.
In this study, we plan to enroll 60 type II and III SMA patients and conduct a single-center, randomized, double-blind, placebo-controlled, prospective trial of two-year duration to evaluate the efficacy and safety of HU.The primary end points are the changes in full-length SMN expression, SMN protein, motor function and lung function in SMA patients. We also design a safety monitoring system to investigate the adverse effects and to assure the patients' safety. We hope we can find and prove the efficacy and safety of HU in SMA patients and set up a evaluating model for multi-center trials in the future.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- Hydroxyurea
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2007 (estimated)
- Study startJun 2007
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by Kaohsiung Medical University Chung-Ho Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Investigators
- Yuh Jyh Jong, MD, Principal investigator, Vice President, Kaohsiung Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00485511
- Sponsor's protocol ID
- DOH96-TD-I-111-TM103
- Status last verified
- Feb 2010
- First submitted
- 11 Jun 2007
- Last updated
- 15 Feb 2010
- Results posted
- No
Publications
Grzeschik SM, Ganta M, Prior TW, Heavlin WD, Wang CH. Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells. Ann Neurol. 2005 Aug;58(2):194-202. doi: 10.1002/ana.20548.
PubMed 16049920
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Trial of Hydroxyurea in Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT00485511
- Acronym / sponsor ID
- DOH96-TD-I-111-TM103
- Conditions
- Spinal Muscular Atrophy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Lead sponsor
- Kaohsiung Medical University Chung-Ho Memorial HospitalUniversity, hospital or other
- Study start
- Jun 2007
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 13 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Spinal muscular atrophy (SMA) is an autosomal recessive disorder in humans which results in the loss of motor neurons. It is caused by reduced levels of the survival motor neuron (SMN) protein as a result of loss or mutation of the SMN1 gene. SMN protein is encoded by two genes, SMN1 and SMN2, which essentially differ by an single nucleotide in exon 7. As a result, the majority of the transcript from SMN2 lacks exon 7. According to clinical severity, SMA was classified to three types, including type I, type II, and type III.
Drugs capable of modifying the transcription pattern of SMN2 to increase the full-length of SMN mRNA expression and the amount of SMN protein may have therapeutic effects for SMA patients. In order to test this hypothesis, we used EBV-transformed lymphoblastoid cell lines derived from the different types of SMA patients to screen the effect of various drugs on SMN2 gene expression. Hydroxyurea (HU) was found to be effective among the drugs we tested. HU is an effective therapeutic agent for patients with thalassemia and sickle cell disease which the toxicity is minimal and is well-tolerated and safely used in children. We had undergone a small-scaled 33 SMA patients randomized pilot trial (HU treatment for 8 weeks and then follow up drug-free 8 weeks) to evaluate the effect of HU in SMA patients and we got a promising preliminary data. We found that HU could significantly increase in the manual muscle testing scores at 4 weeks, and full-length SMN mRNA level in the 30mg/kg/day subgroup at 8 weeks relative to baseline, and it is safe under the dose 30mg/kg/day.
In this study, we plan to enroll 60 type II and III SMA patients and conduct a single-center, randomized, double-blind, placebo-controlled, prospective trial of two-year duration to evaluate the efficacy and safety of HU.The primary end points are the changes in full-length SMN expression, SMN protein, motor function and lung function in SMA patients. We also design a safety monitoring system to investigate the adverse effects and to assure the patients' safety. We hope we can find and prove the efficacy and safety of HU in SMA patients and set up a evaluating model for multi-center trials in the future.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Sixty SMA patients fulfilled the diagnostic criteria of SMA as defined by the International SMA Consortium (Munsat, 1992), and all had homozygous deletion of SMN1 gene but carried SMN2 gene (Chang, 1995; 1997)
- The subjects shall each have the age older than 4 years.
- The subjects (if age > 20 years old) or their parents (if subject age < 20 years old) shall agree with the trial and have signed the informed consents.
Key exclusion criteria (7 listed)
- The subjects shall not have hematological diseases, other severe systemic diseases and congenital anomalies except for SMA.
- The subjects shall not have severe perinatal asphyxia history.
- The subjects shall not be with respiratory assists.
- The subjects shall have normal hepatic and renal functions in the pre-trial examination.
- The subjects shall not have received operation with generalized anesthesia in past half a year.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxyurea | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2010.
- Background: PubMed 16049920Grzeschik SM, Ganta M, Prior TW, Heavlin WD, Wang CH. Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells. Ann Neurol. 2005 Aug;58(2):194-202. doi: 10.1002/ana.20548.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuh Jyh Jong, MD principal investigator
Vice President, Kaohsiung Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Hydroxyurea in people with Spinal Muscular Atrophy, run by Kaohsiung Medical University Chung-Ho Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00485511, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2010.