Multiple System AtrophyPhase 3NCT00211224
Neuroprotection and Natural History in Parkinson's Plus Syndromes (NNIPPS)
A Phase 3 study testing Riluzole in people with Multiple System Atrophy and Progressive Supranuclear Palsy, run by King's College London at 1 site in United Kingdom.
Trial summary
NNIPPS is a clinical trial of riluzole (a drug previously shown to slow down the rate of progression og amyotrophic lateral sclerosis-ALS; Lou Gehrig's disease) involving nearly 800 people diagnosed with the 'parkinson plus' syndromes of multiple system atrophy (MSA) and progressive supranuclear plasy (PSP). Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Multiple System Atrophy, Progressive Supranuclear Palsy
- What is being tested?
- Riluzole
- How many people
- 800 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2000to Nov 2004
- Phase
- Phase 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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- akinetic rigid syndrome plus clinical criteria for MSA or PSP
Who cannot join
- Idiopathic Parkinson's disease
- Other neurological or serious medical disorders
- Unable to give informed consent
- dementia
- liver damage
- women of child bearing age unable to use effective method of contraception
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Institute of Psychiatry, King's College London
London, London, SE58AF
About this study
Official title: Phase 3 Study of Riluzole in Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) (Parkinson's Plus Syndromes)
NNIPPS is a clinical trial of riluzole (a drug previously shown to slow down the rate of progression og amyotrophic lateral sclerosis-ALS; Lou Gehrig's disease) involving nearly 800 people diagnosed with the 'parkinson plus' syndromes of multiple system atrophy (MSA) and progressive supranuclear plasy (PSP). In addition to showing whether riluzole is helpful in MSA and PSP, NNIPPS will improve criteria for making an accurate and early diagnosis, for assessing the rate of progression, and will advance understanding of the biology of these disabling and progressive neurodegenerative diseases.
Read the detailed description
Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) often present as akinetic-rigid syndromes and in the early stages are difficult to differentiate in the clinic. Current Consensus Diagnostic Criteria based on retrospective studies have high specificity but low sensitivity. The NNIPPS study is an EU-funded multinational (France, UK, Germany) multi-centre academic-led project with four main aims. The first aim is to test the hypothesis that riluzole, which may have generic neuroprotective properties, reduces the risk of death and improves function and quality of life (QL) in patients with MSA and PSP- 'parkinson's plus syndromes'. The second aim is to identify prognostic factors for survival and functional deterioration, and to develop and validate functional rating scales prospectively. The third aim is to investigate MRI, cognitive, pathological and genetic aspects of these disorders in relation to disease progression and pathogenesis. The fourth aim is to understand the impact of these diseases on the QL of patients and carers and to identify the health costs of treatment.
The study is designed as a randomised, stratified, controlled trial of the efficacy and safety of riluzole (up to 200mg daily) versus placebo in MSA and PSP. The primary outcome measure is survival at 36 months. Power calculations suggested that we would need to recruit ~400 patients into each stratum (MSA, PSP) in order to detect a reduction in the relative risk (RR) of death at 36 months with 80% power and two-sided a=0.05. Using modified consensus criteria (to provide greater sensitivity) we recruited 766 patients (363 PSP, 404 MSA) over 2 years (1999-2001). The first patients recruited are about to enter the open-label study. The final analysis of the primary efficacy measure is planned for December 2005. Secondary outcome measures include safety, rate of change in UPDRS and other rating scales including a parkinson's plus symtoms rating scale (PPSS), changes in cognitive function assessed using the Mattis Dementia Rating Scale, the Frontal Assessment Battery, The Bushke Selective Reminding Test, The Neuropsychiatric Inventory, and other tests of memory and executive function. QL and Health economic data is collected using the SF36 and a Client Service Receipt Inventory (CSRI). Assessments are made at 6 monthly intervals. Standardised MRI has been acquired in ~70% of cases at entry and will be repeated at 36 months where possible. DNA has been collected from ~75% of cases. 100 brains have been donated and are being analysed using a standardised protocol.
- Being tested
- Riluzole
- Keywords
- multiple system atrophy, progressive supranuclear palsy, riluzole, MSA, PSP
- Medical subject headings
- Multiple System Atrophy, Supranuclear Palsy, Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
survival
Secondary outcomes (3)
functional measures (UPDRS, Parkinson's Plus Scale)
Change in MRI abnormalities
Cognitive changes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startApr 2000
- Study completionNov 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Multiple System AtrophyStudies of the same condition, open and under way.
- More trials run by King's College LondonThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 800 participants
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris, University of Ulm, Aventis Pharmaceuticals
- Investigators
- Peter N Leigh, PhD FRCP, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00211224
- Sponsor's protocol ID
- QLG1-2000-01262
- Other IDs
- European Commission, QLG1-2000-01262
- Status last verified
- Sep 2005
- First submitted
- 13 Sep 2005
- Last updated
- 15 Dec 2005
- Results posted
- No
Publications
Payan CA, Viallet F, Landwehrmeyer BG, Bonnet AM, Borg M, Durif F, Lacomblez L, Bloch F, Verny M, Fermanian J, Agid Y, Ludolph AC, Leigh PN, Bensimon G; NNIPPS Study Group. Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale. PLoS One. 2011;6(8):e22293. doi: 10.1371/journal.pone.0022293. Epub 2011 Aug 4.
PubMed 21829612Rolland Y, Verin M, Payan CA, Duchesne S, Kraft E, Hauser TK, Jarosz J, Deasy N, Defevbre L, Delmaire C, Dormont D, Ludolph AC, Bensimon G, Leigh PN; NNIPPS Study Group. A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability. J Neurol Neurosurg Psychiatry. 2011 Sep;82(9):1025-32. doi: 10.1136/jnnp.2010.214890. Epub 2011 Mar 8.
PubMed 21386111Al-Chalabi A, Durr A, Wood NW, Parkinson MH, Camuzat A, Hulot JS, Morrison KE, Renton A, Sussmuth SD, Landwehrmeyer BG, Ludolph A, Agid Y, Brice A, Leigh PN, Bensimon G; NNIPPS Genetic Study Group. Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS One. 2009 Sep 22;4(9):e7114. doi: 10.1371/journal.pone.0007114.
PubMed 19771175Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C, Leigh PN; NNIPPS Study Group. Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain. 2009 Jan;132(Pt 1):156-71. doi: 10.1093/brain/awn291. Epub 2008 Nov 23.
PubMed 19029129
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Study of Riluzole in Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) (Parkinson's Plus Syndromes)
- ClinicalTrials.gov ID
- NCT00211224
- Acronym / sponsor ID
- QLG1-2000-01262
- Keywords
- multiple system atrophy, progressive supranuclear palsy, riluzole, MSA, PSP
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 800 participants
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- Assistance Publique - Hôpitaux de Paris, University of Ulm, Aventis Pharmaceuticals
- Study start
- Apr 2000
- Study completion
- Nov 2004
- First posted
- 21 Sep 2005 (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.
NNIPPS is a clinical trial of riluzole (a drug previously shown to slow down the rate of progression og amyotrophic lateral sclerosis-ALS; Lou Gehrig's disease) involving nearly 800 people diagnosed with the 'parkinson plus' syndromes of multiple system atrophy (MSA) and progressive supranuclear plasy (PSP). In addition to showing whether riluzole is helpful in MSA and PSP, NNIPPS will improve criteria for making an accurate and early diagnosis, for assessing the rate of progression, and will advance understanding of the biology of these disabling and progressive neurodegenerative diseases.
Detailed description
Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) often present as akinetic-rigid syndromes and in the early stages are difficult to differentiate in the clinic. Current Consensus Diagnostic Criteria based on retrospective studies have high specificity but low sensitivity. The NNIPPS study is an EU-funded multinational (France, UK, Germany) multi-centre academic-led project with four main aims. The first aim is to test the hypothesis that riluzole, which may have generic neuroprotective properties, reduces the risk of death and improves function and quality of life (QL) in patients with MSA and PSP- 'parkinson's plus syndromes'. The second aim is to identify prognostic factors for survival and functional deterioration, and to develop and validate functional rating scales prospectively. The third aim is to investigate MRI, cognitive, pathological and genetic aspects of these disorders in relation to disease progression and pathogenesis. The fourth aim is to understand the impact of these diseases on the QL of patients and carers and to identify the health costs of treatment.
The study is designed as a randomised, stratified, controlled trial of the efficacy and safety of riluzole (up to 200mg daily) versus placebo in MSA and PSP. The primary outcome measure is survival at 36 months. Power calculations suggested that we would need to recruit ~400 patients into each stratum (MSA, PSP) in order to detect a reduction in the relative risk (RR) of death at 36 months with 80% power and two-sided a=0.05. Using modified consensus criteria (to provide greater sensitivity) we recruited 766 patients (363 PSP, 404 MSA) over 2 years (1999-2001). The first patients recruited are about to enter the open-label study. The final analysis of the primary efficacy measure is planned for December 2005. Secondary outcome measures include safety, rate of change in UPDRS and other rating scales including a parkinson's plus symtoms rating scale (PPSS), changes in cognitive function assessed using the Mattis Dementia Rating Scale, the Frontal Assessment Battery, The Bushke Selective Reminding Test, The Neuropsychiatric Inventory, and other tests of memory and executive function. QL and Health economic data is collected using the SF36 and a Client Service Receipt Inventory (CSRI). Assessments are made at 6 monthly intervals. Standardised MRI has been acquired in ~70% of cases at entry and will be repeated at 36 months where possible. DNA has been collected from ~75% of cases. 100 brains have been donated and are being analysed using a standardised protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- akinetic rigid syndrome plus clinical criteria for MSA or PSP
Key exclusion criteria (6 listed)
- Idiopathic Parkinson's disease
- Other neurological or serious medical disorders
- Unable to give informed consent
- dementia
- liver damage
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 |
|---|---|---|
| Riluzole | Drug | – |
Primary outcome
survival
3 secondary outcomes
functional measures (UPDRS, Parkinson's Plus Scale)
Change in MRI abnormalities
Cognitive changes
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2005.
- Derived from this study: PubMed 21829612Payan CA, Viallet F, Landwehrmeyer BG, Bonnet AM, Borg M, Durif F, Lacomblez L, Bloch F, Verny M, Fermanian J, Agid Y, Ludolph AC, Leigh PN, Bensimon G; NNIPPS Study Group. Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale. PLoS One. 2011;6(8):e22293. doi: 10.1371/journal.pone.0022293. Epub 2011 Aug 4.
- Derived from this study: PubMed 21386111Rolland Y, Verin M, Payan CA, Duchesne S, Kraft E, Hauser TK, Jarosz J, Deasy N, Defevbre L, Delmaire C, Dormont D, Ludolph AC, Bensimon G, Leigh PN; NNIPPS Study Group. A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability. J Neurol Neurosurg Psychiatry. 2011 Sep;82(9):1025-32. doi: 10.1136/jnnp.2010.214890. Epub 2011 Mar 8.
- Derived from this study: PubMed 19771175Al-Chalabi A, Durr A, Wood NW, Parkinson MH, Camuzat A, Hulot JS, Morrison KE, Renton A, Sussmuth SD, Landwehrmeyer BG, Ludolph A, Agid Y, Brice A, Leigh PN, Bensimon G; NNIPPS Genetic Study Group. Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS One. 2009 Sep 22;4(9):e7114. doi: 10.1371/journal.pone.0007114.
- Derived from this study: PubMed 19029129Bensimon G, Ludolph A, Agid Y, Vidailhet M, Payan C, Leigh PN; NNIPPS Study Group. Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain. 2009 Jan;132(Pt 1):156-71. doi: 10.1093/brain/awn291. Epub 2008 Nov 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.
Peter N Leigh, PhD FRCP principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Riluzole in people with Multiple System Atrophy and Progressive Supranuclear Palsy, run by King's College London at 1 site in United Kingdom.
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 1 inclusion and 6 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: stopped early, as of the sponsor's last update on 15 Dec 2005. 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 United Kingdom. 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 phase mean?
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 was stopped early. Results are not available in the source record.
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?
survival. 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 NCT00211224, which also lists 4 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 15 Dec 2005.