Spinocerebellar Ataxia Type 1BIOSCANCT01470729
Biomarkers in Autosomal Dominant Cerebellar Ataxia
An observational study of Spinocerebellar Ataxia Type 1 and Spinocerebellar Ataxia Type 2, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders that are clinically and genetically various. BIOSCA study aims to identify markers of the metabolism (energy production inside the cells) in the blood and the brain of ADCA 1,2,3 and 7 patients and control subjects, in the… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia, Autosomal Recessive 3
- What is being tested?
- metabolic and imaging biomarkers in SCA1,2,3 and 7 patients
- How many people
- 102 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2011to Dec 2015
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Spinocerebellar Ataxia Type 1 (SCA1) Spinocerebellar Ataxia Type 2 (SCA2) Spinocerebellar Ataxia Type 3 (SCA3) Spinocerebellar Ataxia Type 7 (SCA7)
Who may be able to join
- More than 18 years of age
- Ability to tolerate MRI
- Positive genetic test to SCA1, 2, 3 or 7
- Coverage by social insurance
- Written informed consent must be obtained from the subject
Who cannot join
- Less than 18 years of age
- Concomitant significant neurological disorder
- Unsuitability for MRI, e.g. claustrophobia, metal implants
- History of significant head injury
- Unability to receive an informed explanation about the protocol
- Unability to complete the protocol
- Non coverage by social insurance
- No written informed consent obtained
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification of Biomarkers in Patients With Autosomal Dominant Cerebellar Ataxia
Autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders that are clinically and genetically various. BIOSCA study aims to identify markers of the metabolism (energy production inside the cells) in the blood and the brain of ADCA 1,2,3 and 7 patients and control subjects, in the perspective of future therapeutic trials.
Read the detailed description
Rational. Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders caused by unstable CAG repeat expansions encoding polyglutamine tracts. ADCA have a wide range of neurological symptoms including ataxia of gait, stance, and limbs, cerebellar dysarthria, oculomotor disturbances of cerebellar and supranuclear genesis, retinopathy, optic atrophy, spasticity, extra-pyramidal movement disorders, peripheral neuropathy, sphincter disturbances, cognitive impairment, and epilepsy. Corresponding to neuropathological findings in hereditary ataxia, there are three fundamental patterns of degeneration on MRI: spinal atrophy, olivopontocerebellar atrophy, and cortical cerebellar atrophy. We previously showed an hypercatabolism in premanifest and early stage Huntington's disease (HD), along with a systemic metabolic defect: progressive decrease of the plasmatic branched-chain amino acids (BCAA) - correlated with low serum IGF1 (insulin-like growth factor 1) - and muscle energy metabolism abnormalities measured by 31P-NMR spectroscopy. We also observed a weight loss in SCA1, 3 and mostly SCA7 patients. In addition, we underlined in a preliminary study a significant decrease of the BCAA in SCA1,2,3 and 7 patients, suggesting that an energy deficit would also be implied in SCA pathogenesis. Transcriptional interferences are likely a part of SCA physiopathology, as shown in the retinal cells of a SCA7 mouse model, or as we detected over the cerebellum growth of these mice. The hallmark of the gene expression studies in SCA1 and SCA7 mice points out the implication of IGF1 pathway and IGF1 receptor. As in HD, these transcriptional disorders might witness the metabolic defects above-mentioned.
Study objectives. The primary aim of the study is to provide metabolic and imaging biomarkers in SCA1,2,3 and 7 patients and controls in the perspective of future therapeutic trials.
The secondary aims are to determine (i) an systemic energy profile in SCA1,2,3 and 7 patients with the confirmation of an hypercatabolic status, (ii) a brain energy profile in SCA1,2,3 and 7 patients measured by in vivo 31P-NMR spectroscopy.
Study population. BIOSCA will recruit 120 participants in the Pitie Salpetriere University Hospital located in Paris, France. The target cohort will be 80 patients - divided into 4 groups of 20 participants of each mutation - and 40 controls.
Study design. All patients (SCA1,2,3,7) will be assessed at baseline (visit 1), 1 year (visit 2) and 2 years (visit 3). At visit 1 and 3, subjects will undergo clinical, MRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples. Each visit will last approximately 6 hours. At visit 2, they will have only a clinical assessment along with a fasted blood sample. Control subjects will be seen only at visit 1 and 3 with the same assessments as the patients.
Study period. BIOSCA is a prospective study for which each participant is enrolled for 24 months. The study duration is 36 months. The start date is November 2011.
Funding. BIOSCA is funded by a national funding hospital program in clinical research (PHRC) from APHP institution.
- Conditions
- Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia, Autosomal Recessive 3, Episodic Ataxia, Type 7
- Being tested
- metabolic and imaging biomarkers in SCA1,2,3 and 7 patients
- Keywords
- Spinocerebellar ataxia, energy metabolism, NMR spectroscopy
- Medical subject headings
- Spinocerebellar Ataxias, Spinocerebellar ataxia, autosomal recessive 3, Episodic Ataxia, Type 7
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metabolic and imaging biomarkers in SCA1,2,3 and 7 patientsOther
MRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples
| Study group | Role | What they receive |
|---|---|---|
| Spinocerebellar Ataxia type 1 (SCA1) | Spinocerebellar Ataxia type 1 (SCA1) Receives: Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients | |
| Spinocerebellar Ataxia type 2 (SCA2) | Spinocerebellar Ataxia type 2 (SCA2) Receives: Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients | |
| Spinocerebellar Ataxia type 3 (SCA3) | Spinocerebellar Ataxia type 3 (SCA3) Receives: Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients | |
| Spinocerebellar Ataxia type 7 (SCA7) | Spinocerebellar Ataxia type 7 (SCA7) Receives: Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
metabolic biomarkers of SCA
Measured: 12 months or 24 months
Secondary outcomes (1)
imaging biomarkers of SCA
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Spinocerebellar Ataxia Type 1Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Other
- Time perspective
- Prospective
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexandra DURR, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01470729
- Sponsor's protocol ID
- P100125
- Acronym
- BIOSCA
- Status last verified
- Jun 2014
- First submitted
- 9 Nov 2011
- Last updated
- 6 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Adanyeguh IM, Henry PG, Nguyen TM, Rinaldi D, Jauffret C, Valabregue R, Emir UE, Deelchand DK, Brice A, Eberly LE, Oz G, Durr A, Mochel F. In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7. Mov Disord. 2015 Apr 15;30(5):662-70. doi: 10.1002/mds.26181. Epub 2015 Mar 15.
PubMed 25773989Adanyeguh IM, Perlbarg V, Henry PG, Rinaldi D, Petit E, Valabregue R, Brice A, Durr A, Mochel F. Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes. Neuroimage Clin. 2018 Jun 14;19:858-867. doi: 10.1016/j.nicl.2018.06.011. eCollection 2018.
PubMed 29922574Garali I, Adanyeguh IM, Ichou F, Perlbarg V, Seyer A, Colsch B, Moszer I, Guillemot V, Durr A, Mochel F, Tenenhaus A. A strategy for multimodal data integration: application to biomarkers identification in spinocerebellar ataxia. Brief Bioinform. 2018 Nov 27;19(6):1356-1369. doi: 10.1093/bib/bbx060.
PubMed 29106465Faber J, Schaprian T, Berkan K, Reetz K, Franca MC Jr, de Rezende TJR, Hong J, Liao W, van de Warrenburg B, van Gaalen J, Durr A, Mochel F, Giunti P, Garcia-Moreno H, Schoels L, Hengel H, Synofzik M, Bender B, Oz G, Joers J, de Vries JJ, Kang JS, Timmann-Braun D, Jacobi H, Infante J, Joules R, Romanzetti S, Diedrichsen J, Schmid M, Wolz R, Klockgether T. Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3. Mov Disord. 2021 Oct;36(10):2273-2281. doi: 10.1002/mds.28610. Epub 2021 May 5.
PubMed 33951232Coarelli G, Darios F, Petit E, Dorgham K, Adanyeguh I, Petit E, Brice A, Mochel F, Durr A. Plasma neurofilament light chain predicts cerebellar atrophy and clinical progression in spinocerebellar ataxia. Neurobiol Dis. 2021 Jun;153:105311. doi: 10.1016/j.nbd.2021.105311. Epub 2021 Feb 23.
PubMed 33636389
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Biomarkers in Patients With Autosomal Dominant Cerebellar Ataxia
- ClinicalTrials.gov ID
- NCT01470729
- Acronym / sponsor ID
- BIOSCA / P100125
- Conditions
- Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia, Autosomal Recessive 3, Episodic Ataxia, Type 7
- Keywords
- Spinocerebellar ataxia, energy metabolism, NMR spectroscopy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 11 Nov 2011 (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.
Autosomal dominant cerebellar ataxias (ADCA) are a group of neurodegenerative disorders that are clinically and genetically various. BIOSCA study aims to identify markers of the metabolism (energy production inside the cells) in the blood and the brain of ADCA 1,2,3 and 7 patients and control subjects, in the perspective of future therapeutic trials.
Detailed description
Rational. Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders caused by unstable CAG repeat expansions encoding polyglutamine tracts. ADCA have a wide range of neurological symptoms including ataxia of gait, stance, and limbs, cerebellar dysarthria, oculomotor disturbances of cerebellar and supranuclear genesis, retinopathy, optic atrophy, spasticity, extra-pyramidal movement disorders, peripheral neuropathy, sphincter disturbances, cognitive impairment, and epilepsy. Corresponding to neuropathological findings in hereditary ataxia, there are three fundamental patterns of degeneration on MRI: spinal atrophy, olivopontocerebellar atrophy, and cortical cerebellar atrophy. We previously showed an hypercatabolism in premanifest and early stage Huntington's disease (HD), along with a systemic metabolic defect: progressive decrease of the plasmatic branched-chain amino acids (BCAA) - correlated with low serum IGF1 (insulin-like growth factor 1) - and muscle energy metabolism abnormalities measured by 31P-NMR spectroscopy. We also observed a weight loss in SCA1, 3 and mostly SCA7 patients. In addition, we underlined in a preliminary study a significant decrease of the BCAA in SCA1,2,3 and 7 patients, suggesting that an energy deficit would also be implied in SCA pathogenesis. Transcriptional interferences are likely a part of SCA physiopathology, as shown in the retinal cells of a SCA7 mouse model, or as we detected over the cerebellum growth of these mice. The hallmark of the gene expression studies in SCA1 and SCA7 mice points out the implication of IGF1 pathway and IGF1 receptor. As in HD, these transcriptional disorders might witness the metabolic defects above-mentioned.
Study objectives. The primary aim of the study is to provide metabolic and imaging biomarkers in SCA1,2,3 and 7 patients and controls in the perspective of future therapeutic trials.
The secondary aims are to determine (i) an systemic energy profile in SCA1,2,3 and 7 patients with the confirmation of an hypercatabolic status, (ii) a brain energy profile in SCA1,2,3 and 7 patients measured by in vivo 31P-NMR spectroscopy.
Study population. BIOSCA will recruit 120 participants in the Pitie Salpetriere University Hospital located in Paris, France. The target cohort will be 80 patients - divided into 4 groups of 20 participants of each mutation - and 40 controls.
Study design. All patients (SCA1,2,3,7) will be assessed at baseline (visit 1), 1 year (visit 2) and 2 years (visit 3). At visit 1 and 3, subjects will undergo clinical, MRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples. Each visit will last approximately 6 hours. At visit 2, they will have only a clinical assessment along with a fasted blood sample. Control subjects will be seen only at visit 1 and 3 with the same assessments as the patients.
Study period. BIOSCA is a prospective study for which each participant is enrolled for 24 months. The study duration is 36 months. The start date is November 2011.
Funding. BIOSCA is funded by a national funding hospital program in clinical research (PHRC) from APHP institution.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Spinocerebellar Ataxia type 1 (SCA1) | – | Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patientsSpinocerebellar Ataxia type 1 (SCA1) |
| Spinocerebellar Ataxia type 2 (SCA2) | – | Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patientsSpinocerebellar Ataxia type 2 (SCA2) |
| Spinocerebellar Ataxia type 3 (SCA3) | – | Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patientsSpinocerebellar Ataxia type 3 (SCA3) |
| Spinocerebellar Ataxia type 7 (SCA7) | – | Other: metabolic and imaging biomarkers in SCA1,2,3 and 7 patientsSpinocerebellar Ataxia type 7 (SCA7) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Spinocerebellar Ataxia Type 1 (SCA1) Spinocerebellar Ataxia Type 2 (SCA2) Spinocerebellar Ataxia Type 3 (SCA3) Spinocerebellar Ataxia Type 7 (SCA7)
Key inclusion criteria (5 listed)
- More than 18 years of age
- Ability to tolerate MRI
- Positive genetic test to SCA1, 2, 3 or 7
- Coverage by social insurance
- Written informed consent must be obtained from the subject
Key exclusion criteria (8 listed)
- Less than 18 years of age
- Concomitant significant neurological disorder
- Unsuitability for MRI, e.g. claustrophobia, metal implants
- History of significant head injury
- Unability to receive an informed explanation about the protocol
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 |
|---|---|---|
| metabolic and imaging biomarkers in SCA1,2,3 and 7 patientsMRI, a bone mineral density and a resting metabolic rate assessments, as well as donating fasted blood samples | Other | Spinocerebellar Ataxia type 1 (SCA1), Spinocerebellar Ataxia type 2 (SCA2), Spinocerebellar Ataxia type 3 (SCA3), Spinocerebellar Ataxia type 7 (SCA7) |
Primary outcome
metabolic biomarkers of SCA
Time frame: 12 months or 24 months
1 secondary outcome
imaging biomarkers of SCA
Time frame: 24 months
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 6 Sep 2019.
- Results publication: PubMed 25773989Adanyeguh IM, Henry PG, Nguyen TM, Rinaldi D, Jauffret C, Valabregue R, Emir UE, Deelchand DK, Brice A, Eberly LE, Oz G, Durr A, Mochel F. In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7. Mov Disord. 2015 Apr 15;30(5):662-70. doi: 10.1002/mds.26181. Epub 2015 Mar 15.
- Results publication: PubMed 29922574Adanyeguh IM, Perlbarg V, Henry PG, Rinaldi D, Petit E, Valabregue R, Brice A, Durr A, Mochel F. Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes. Neuroimage Clin. 2018 Jun 14;19:858-867. doi: 10.1016/j.nicl.2018.06.011. eCollection 2018.
- Results publication: PubMed 29106465Garali I, Adanyeguh IM, Ichou F, Perlbarg V, Seyer A, Colsch B, Moszer I, Guillemot V, Durr A, Mochel F, Tenenhaus A. A strategy for multimodal data integration: application to biomarkers identification in spinocerebellar ataxia. Brief Bioinform. 2018 Nov 27;19(6):1356-1369. doi: 10.1093/bib/bbx060.
- Derived from this study: PubMed 33951232Faber J, Schaprian T, Berkan K, Reetz K, Franca MC Jr, de Rezende TJR, Hong J, Liao W, van de Warrenburg B, van Gaalen J, Durr A, Mochel F, Giunti P, Garcia-Moreno H, Schoels L, Hengel H, Synofzik M, Bender B, Oz G, Joers J, de Vries JJ, Kang JS, Timmann-Braun D, Jacobi H, Infante J, Joules R, Romanzetti S, Diedrichsen J, Schmid M, Wolz R, Klockgether T. Regional Brain and Spinal Cord Volume Loss in Spinocerebellar Ataxia Type 3. Mov Disord. 2021 Oct;36(10):2273-2281. doi: 10.1002/mds.28610. Epub 2021 May 5.
- Derived from this study: PubMed 33636389Coarelli G, Darios F, Petit E, Dorgham K, Adanyeguh I, Petit E, Brice A, Mochel F, Durr A. Plasma neurofilament light chain predicts cerebellar atrophy and clinical progression in spinocerebellar ataxia. Neurobiol Dis. 2021 Jun;153:105311. doi: 10.1016/j.nbd.2021.105311. Epub 2021 Feb 23.
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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.
Alexandra DURR, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Spinocerebellar Ataxia Type 1 and Spinocerebellar Ataxia Type 2, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 5 inclusion and 8 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 6 Sep 2019. 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 France. 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 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.
What does the primary outcome measure?
metabolic biomarkers of SCA (time frame: 12 months or 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01470729, which also lists 5 linked publications.
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 6 Sep 2019.