XlsmaNCT03649919
Multi-center Clinical Study on the Diagnosis and Treatment Management of Rare Neurological Disease in Children
An observational study of Xlsma and DMD, run by Children's Hospital of Fudan University at 1 site in China.
Trial summary
The incidence of rare diseases is extremely low, the disease is numerous, the symptoms are serious, and the detection technology is complicated. Countries have different definitions of rare diseases. Read more about this study
- Who is it for?
- Ages Up to 18 years
- How many people
- 0 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2021to 30 Dec 2021
- Phase
- Observational
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patient affected with Xlsma, DMD, X-ALD or TSC aged frome 0 to 18 years old.
Who may be able to join
None listed.
Who cannot join
- -
- 2. DMD:
- Inclusion criteria: patients meet the all the following criteria:
- Clinically manifestation: weakness, clumsiness, a Gowers' sign, difficulty with stair climbing, or toe walking. developmental delay or increased concentrations of serum enzymes such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, or very high creatine kinase level.
- Dystrophin gene mutation: dystrophin gene deletion and duplication testing is usually the first confirmatory test best done by MLPA or comparative genomic hybridisation array. Approximately 70% of individuals with DMD have a single-exon or multi-exon deletion or duplication in the dystrophin gene. If deletion or duplication testing is negative, genetic sequencing should be done to screen for the remaining types of mutations that are attributed to DMD (approximately 25-30%).
- Muscle biopsy: if genetic testing does not confirm a clinical diagnosis of DMD, then a muscle biopsy sample should be tested for the presence of dystrophin protein by immunohistochemistry of tissue cryosections or by western blot of a muscle protein extract. Muscle samples from DMD patient has no dystrophin present, while BMD Becker muscular dystrophy (with some partially functional dystrophin present).
Show all 22Show fewer
- 3. X-ALD:
- Inclusion criteria: patients meet the all the following criteria:
- 1. Clinically manifestation:
- Attention deficit disorder or hyperactivity; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within six months to two years.
- Adrenomyeloneuropathy (AMN) manifests as progressive stiffness and weakness of the legs, sphincter disturbances, sexual dysfunction, and often, impaired adrenocortical function; all symptoms are progressive over decades, most commonly in an individual in his twenties or middle age.
- Magnetic resonance imaging shows cerebral demyelination.
- 2. Dystrophin gene mutation: The diagnosis of X-ALD is usually established in a female proband with detection of a heterozygous ABCD1 pathogenic variant and elevated VLCFA.
- 4. TSC:
- Inclusion criteria:patients meet the all the following criteria:
- Clinical diagnostic criteria:
- Major features: (1) Hypomelanotic macules (≥3, at least 5-mm diameter). (2) Angiofibromas (≥3) or fibrous cephalic plaque. (3) Ungual fibromas (≥2). (4) Shagreen patch. (5) Multiple retinal hamartomas. (6) Cortical dysplasias. (7) Subependymal nodules. (8) Subependymal giant cell astrocytoma. (9) Cardiac rhabdomyoma. (10) Lymphangioleiomyomatosis (LAM). (11) Angiomyolipomas (≥2).
- Minor features: (1)"Confetti" skin lesions. (2) Dental enamel pits (>3). (3) Intraoral fibromas (≥2). (4) Retinal achromic patch. (5) Multiple renal cysts. (6) Nonrenal hamartomas.
- Two major features or one major feature with ≥2 minor features can diagnose. Either one major feature or ≥2 minor features can diagnosis possibly.
- Genetic diagnostic criteria:
- The identification of either a TSC1 or TSC2 pathogenic mutation in DNA from normal tissue is sufficient to make a definite diagnosis of TSC.
- -
Trial locations and contacts
1 site in 1 country.
About this study
The incidence of rare diseases is extremely low, the disease is numerous, the symptoms are serious, and the detection technology is complicated. Countries have different definitions of rare diseases. The definition of rare diseases in China is defined as: diseases with a prevalence of less than 1 in 500 000 or newborns with an incidence of less than 1/10 000 are rare diseases. Due to the low incidence of rare diseases and the accumulation of multiple organs and systems in most diseases, clinicians lack comprehensive and systematic understanding. Patients often face great difficulties in seeking medical treatment and diagnosis. Currently, there is a lack of systematic and rare diseases in China. Management, diagnosis and treatment of rare diseases, making the diagnosis of rare diseases, prevention interventions seriously lagging behind, obviously behind the management of developed countries and regions; rare diseases are mostly related to genetic variation, with the clinical application of genetic diagnosis technology, more and more Many genetically related rare diseases have been diagnosed at an early stage; at present, precision medicine is rapidly developing, and more and more rare disease clinical trials have entered the country, bringing prospects for the treatment of rare diseases. For this reason, the management of rare diseases is particularly important.
At present, some rare diseases of the nervous system can be treated early; for example, immune-related rare diseases have common normative immunotherapy and functional disability prevention, and the characteristics of single disease management of each disease; hereditary degenerative rare diseases such as progressive 2-3 multi-center clinical trials of spinal muscular atrophy and progressive muscular dystrophy have been entered into our hospital (in our hospital), X-linked pre-diagnosis of adrenal malnutrition genetic diseases, and appropriate treatment time is selected. Stem cell transplantation is in research and planning; the long-term management and comprehensive treatment of nodular sclerosis and Dravet syndrome are important for the prevention and treatment of diseases; therefore, the early diagnosis, pathogenesis and standardized treatment of rare diseases of the nervous system are urgent. And necessity.
- Medical subject headings
- Arthrogryposis multiplex congenita, distal, X-linked, Adrenoleukodystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Other
Patients receive routine diagnostic and treatment medications.
| Study group | Role | What they receive |
|---|---|---|
| 1 spinal muscular atrophy, SMA | Progressive muscular atrophy (SMA) is a group of autosomal recessive neuromuscular diseases characterized by degeneration of the anterior horn cells of the spinal cord, which is characterized by progressive generalized muscle weakness and muscle atrophy. The incidence of SMA is about 1/11000, and the occurrence of SMA is caused by mutation of the SMN1 gene. SMA can be classified into type I-III according to age of onset, maximum muscle activity, and survival. | |
| 2 DMD | Progressive muscular dystrophy (DMD) is a group of hereditary skeletal muscle degeneration diseases. It is clinically characterized by slow and progressive development of muscle atrophy and muscle weakness. The inheritance can be divided into sexual chain recessiveness. Genetic type. For children with high suspected DMD/BMD, the current DMD diagnosis is preferred by MLPA method for detection of DNA in peripheral blood; MLPA diagnostic kit can only detect about 65% of large gene deletions or repeat types, thus detecting undetected gene mutations. | |
| 3 X-linked adrenoleukodystrophy X-ALD | X-linked adrenoleukodystrophy X-ALD is an X-linked episode of a group of diseases characterized by progressive central nervous system demyelination and adrenal insufficiency. About 1/20000 male children. Most cases of X-ALD are treated for neurological symptoms for the first time, most of them start from 3-10 years old. Early manifestations include slow mental function, decreased academic performance, lack of interest or hyperactivity, difficulty in speech, difficulty in articulation, etc. Visual impairment and progressive hemiplegia are more common symptoms. | |
| 4 tuberous sclerosis complex，TSC | Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease involving multiple systems. About 1 in every 6,000-10,000 people in TSC suffer from tuberous sclerosis, and children in the neurology department are diagnosed with developmental delay or seizures, and about 2/3 have no positive family history. Nearly 2 million people worldwide suffer from TSC, and there are about 200,000 in China. |
What is being measured
The primary outcome is the main question the study is designed to answer.
spinal muscular atrophy, SMA
Diagnosed based on the clinical criteria and genetic analysis. The details clinical diagnosis refer to the inclusion criteria. The genetic diagnosis of a Spinal Muscular Atrophy is established in a patient by identification of a homozygous absence of SMN1 exon 7 using SMA MLPA test (MRC-holland P021-A2).
Measured: from birth, to 18 years old
DMD
Diagnosed based on the clinical criteria and genetic analysis. The details clinical diagnosis refer to the inclusion criteria. The genetic diagnosis of a Dystrophinopathy is established in a male patient by identification of a hemizygous pathogenic variant (including exon or whole-gene deletions/duplications, intragenic deletions/insertions, missense, nonsense, and splice site variants) in DMD gene using a multigene panel sequencing test (Agilent ClearSeq Inherited Disease panel kit).
Measured: from birth, to 18 years old
X-linked adrenoleukodystrophy X-ALD
Diagnosed based on the clinical criteria and the details clinical diagnosis refer to the inclusion criteria.
Measured: from birth, to 18 years old
tuberous sclerosis complex，TSC
Diagnosed based on the clinical criteria and genetic analysis. The details clinical diagnosis refer to the inclusion criteria. The genetic diagnosis of a TSC is established in a patient by identification of a heterozygous pathogenic variant (including exon or whole-gene deletions, intragenic deletions/insertions, missense, nonsense, and splice site variants) in TSC1 or TSC2 using a multigene panel sequencing test (Agilent ClearSeq Inherited Disease panel kit).
Measured: from birth, to 18 years old
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2018
- Study start30 Sep 2021 (estimated)
- Primary completion30 Oct 2021 (estimated)
- Study completion30 Dec 2021 (estimated)
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for XlsmaStudies of the same condition, open and under way.
- More trials run by Children's Hospital of Fudan UniversityThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Children's Medical Center, Xinhua Hospital of Shanghai Jiaotong University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03649919
- Sponsor's protocol ID
- EKYY-MCSDTMRNDC
- Status last verified
- Aug 2021
- First submitted
- 26 Aug 2018
- Last updated
- 11 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center Clinical Study on the Diagnosis and Treatment Management of Rare Neurological Disease in Children
- ClinicalTrials.gov ID
- NCT03649919
- Acronym / sponsor ID
- EKYY-MCSDTMRNDC
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital of Fudan UniversityUniversity, hospital or other
- Collaborators
- Shanghai Children's Medical Center, Xinhua Hospital of Shanghai Jiaotong University
- Study start
- 30 Sep 2021 (estimated)
- Primary completion
- 30 Oct 2021 (estimated)
- Study completion
- 30 Dec 2021 (estimated)
- First posted
- 28 Aug 2018 (actual)
- 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.
The incidence of rare diseases is extremely low, the disease is numerous, the symptoms are serious, and the detection technology is complicated. Countries have different definitions of rare diseases. The definition of rare diseases in China is defined as: diseases with a prevalence of less than 1 in 500 000 or newborns with an incidence of less than 1/10 000 are rare diseases. Due to the low incidence of rare diseases and the accumulation of multiple organs and systems in most diseases, clinicians lack comprehensive and systematic understanding. Patients often face great difficulties in seeking medical treatment and diagnosis. Currently, there is a lack of systematic and rare diseases in China. Management, diagnosis and treatment of rare diseases, making the diagnosis of rare diseases, prevention interventions seriously lagging behind, obviously behind the management of developed countries and regions; rare diseases are mostly related to genetic variation, with the clinical application of genetic diagnosis technology, more and more Many genetically related rare diseases have been diagnosed at an early stage; at present, precision medicine is rapidly developing, and more and more rare disease clinical trials have entered the country, bringing prospects for the treatment of rare diseases. For this reason, the management of rare diseases is particularly important.
At present, some rare diseases of the nervous system can be treated early; for example, immune-related rare diseases have common normative immunotherapy and functional disability prevention, and the characteristics of single disease management of each disease; hereditary degenerative rare diseases such as progressive 2-3 multi-center clinical trials of spinal muscular atrophy and progressive muscular dystrophy have been entered into our hospital (in our hospital), X-linked pre-diagnosis of adrenal malnutrition genetic diseases, and appropriate treatment time is selected. Stem cell transplantation is in research and planning; the long-term management and comprehensive treatment of nodular sclerosis and Dravet syndrome are important for the prevention and treatment of diseases; therefore, the early diagnosis, pathogenesis and standardized treatment of rare diseases of the nervous system are urgent. And necessity.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 spinal muscular atrophy, SMA | – | –Progressive muscular atrophy (SMA) is a group of autosomal recessive neuromuscular diseases characterized by degeneration of the anterior horn cells of the spinal cord, which is characterized by progressive generalized muscle weakness and muscle atrophy. The incidence of SMA is about 1/11000, and the occurrence of SMA is caused by mutation of the SMN1 gene. SMA can be classified into type I-III according to age of onset, maximum muscle activity, and survival. |
| 2 DMD | – | –Progressive muscular dystrophy (DMD) is a group of hereditary skeletal muscle degeneration diseases. It is clinically characterized by slow and progressive development of muscle atrophy and muscle weakness. The inheritance can be divided into sexual chain recessiveness. Genetic type. For children with high suspected DMD/BMD, the current DMD diagnosis is preferred by MLPA method for detection of DNA in peripheral blood; MLPA diagnostic kit can only detect about 65% of large gene deletions or repeat types, thus detecting undetected gene mutations. |
| 3 X-linked adrenoleukodystrophy X-ALD | – | –X-linked adrenoleukodystrophy X-ALD is an X-linked episode of a group of diseases characterized by progressive central nervous system demyelination and adrenal insufficiency. About 1/20000 male children. Most cases of X-ALD are treated for neurological symptoms for the first time, most of them start from 3-10 years old. Early manifestations include slow mental function, decreased academic performance, lack of interest or hyperactivity, difficulty in speech, difficulty in articulation, etc. Visual impairment and progressive hemiplegia are more common symptoms. |
| 4 tuberous sclerosis complex，TSC | – | –Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease involving multiple systems. About 1 in every 6,000-10,000 people in TSC suffer from tuberous sclerosis, and children in the neurology department are diagnosed with developmental delay or seizures, and about 2/3 have no positive family history. Nearly 2 million people worldwide suffer from TSC, and there are about 200,000 in China. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patient affected with Xlsma, DMD, X-ALD or TSC aged frome 0 to 18 years old.
Key inclusion criteria (0 listed)
Key exclusion criteria (22 listed)
- -
- Clinically manifestation: weakness, clumsiness, a Gowers' sign, difficulty with stair climbing, or toe walking. developmental delay or increased concentrations of serum enzymes such as alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, or very high creatine kinase level.
- Dystrophin gene mutation: dystrophin gene deletion and duplication testing is usually the first confirmatory test best done by MLPA or comparative genomic hybridisation array. Approximately 70% of individuals with DMD have a single-exon or multi-exon deletion or duplication in the dystrophin gene. If deletion or duplication testing is negative, genetic sequencing should be done to screen for the remaining types of mutations that are attributed to DMD (approximately 25-30%).
- Muscle biopsy: if genetic testing does not confirm a clinical diagnosis of DMD, then a muscle biopsy sample should be tested for the presence of dystrophin protein by immunohistochemistry of tissue cryosections or by western blot of a muscle protein extract. Muscle samples from DMD patient has no dystrophin present, while BMD Becker muscular dystrophy (with some partially functional dystrophin present).
- Attention deficit disorder or hyperactivity; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within six months to two years.
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 |
|---|---|---|
| Patients receive routine diagnostic and treatment medications. | Other | 1 spinal muscular atrophy, SMA, 2 DMD, 3 X-linked adrenoleukodystrophy X-ALD, 4 tuberous sclerosis complex，TSC |
Primary outcome
spinal muscular atrophy, SMA
Time frame: from birth, to 18 years old
Diagnosed based on the clinical criteria and genetic analysis. The details clinical diagnosis refer to the inclusion criteria. The genetic diagnosis of a Spinal Muscular Atrophy is established in a patient by identification of a homozygous absence of SMN1 exon 7 using SMA MLPA test (MRC-holland P021-A2).
DMD
Time frame: from birth, to 18 years old
Diagnosed based on the clinical criteria and genetic analysis. The details clinical diagnosis refer to the inclusion criteria. The genetic diagnosis of a Dystrophinopathy is established in a male patient by identification of a hemizygous pathogenic variant (including exon or whole-gene deletions/duplications, intragenic deletions/insertions, missense, nonsense, and splice site variants) in DMD gene using a multigene panel sequencing test (Agilent ClearSeq Inherited Disease panel kit).
X-linked adrenoleukodystrophy X-ALD
Time frame: from birth, to 18 years old
Diagnosed based on the clinical criteria and the details clinical diagnosis refer to the inclusion criteria.
tuberous sclerosis complex，TSC
Time frame: from birth, to 18 years old
Diagnosed based on the clinical criteria and genetic analysis. The details clinical diagnosis refer to the inclusion criteria. The genetic diagnosis of a TSC is established in a patient by identification of a heterozygous pathogenic variant (including exon or whole-gene deletions, intragenic deletions/insertions, missense, nonsense, and splice site variants) in TSC1 or TSC2 using a multigene panel sequencing test (Agilent ClearSeq Inherited Disease panel kit).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2021.
- Individual participant dataSharing planned: Yes
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Xlsma and DMD, run by Children's Hospital of Fudan University at 1 site in China.
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 0 inclusion and 22 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: withdrawn, as of the sponsor's last update on 11 Aug 2021. 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 China. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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.
What does the primary outcome measure?
spinal muscular atrophy, SMA (time frame: from birth, to 18 years old). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Aug 2021.