Neuroprotection and Natural History in Parkinson's Plus Syndromes (NNIPPS)

Multiple System Atrophy Clinical Trial

Official title:

Phase 3 Study of Riluzole in Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) (Parkinson's Plus Syndromes)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00211224
• Other study ID #: QLG1-2000-01262
• Secondary ID: European Commiss
• Status: Terminated
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: December 14, 2005
• Start date: April 2000
• Est. completion date: November 2004

Study information

• Verified date: September 2005
• Source: King's College London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 800
• Est. completion date: November 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• akinetic rigid syndrome plus clinical criteria for MSA or PSP

Exclusion Criteria:

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Progressive Supranuclear Palsy
• Shy-Drager Syndrome
• Supranuclear Palsy, Progressive

Intervention

Drug:
• Riluzole

Locations

Country	Name	City	State
United Kingdom	Institute of Psychiatry, King's College London	London

Sponsors (4)

Lead Sponsor	Collaborator
King's College London	Assistance Publique - Hôpitaux de Paris, Aventis Pharmaceuticals, University of Ulm

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival
Secondary	functional measures (UPDRS, Parkinson's Plus Scale)
Secondary	Change in MRI abnormalities
Secondary	Cognitive changes