Progressive Supranuclear Palsy (PSP)Phase 3RIVA-PSPNCT02839642
Efficacy of RIVAstigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy
A Phase 3 study testing Rivastigmine in people with Progressive Supranuclear Palsy (PSP), run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease from the parkinsonian syndrome group. It represents 5 to 10% of all parkinsonian syndromes and affects 3,000 to 10,000 persons in France. Read more about this study
- Who is it for?
- Ages 41 to 85 years
- Conditions the study is for
- Progressive Supranuclear Palsy (PSP)
- What is being tested?
- Rivastigmine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 106 participants
- Where
- 1 siteFrance
- Study dates
- 26 Jul 2016to 17 Nov 2022
- 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 41 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Probable PSP of the Richardson subtype as defined by the NINDS-SPSP criteria modified so as to allow inclusions of patients who have first fallen within 3 years of disease onset.
- Aged 41 to 80 years at the time of screening
- Judged by site investigator to be able to comply with gait/balance and neuropsychological evaluations at baseline and throughout the study
- Able to ambulate independently or with assistance (cane)
- Score ≥ 20 on the mini-mental state examination (MMSE) at screening
- A reliable caregiver - defined as a person having frequent contact with subject (≥ 3 hours per day) and willing to fill the fall diaries and monitor study medication compliance and the subject's health and concomitant medication throughout the study - must accompany the subject to all visits.
Show all 10Show fewer
- A fall or near fall rate ≥ 2/week in average (estimated through interview at screening and confirmed during a 2-week period between screening and baseline using fall postcards).
- Any parkinsonian medication taken by the subject must be stable in dose for 4 weeks prior to screening and must remain stable for the duration of the study
- Stable on all other chronic medications for 4 weeks prior to screening
- Written informed consent provided by subject and caregiver.
Who cannot join
- Non ambulatory patient.
- History and clinical examination suggesting another parkinsonian syndrome (Parkinson's disease, Dementia with Lewy Bodies, Corticobasal Degeneration, Multisystem Atrophy, Vascular Parkinsonism, tumoral parkinsonism, anti-psychotic drug-induced parkinsonism)
- Presence of other significant neurological or psychiatric disorders: Alzheimer's disease, epilepsy, history of stroke, psychotic disorder, severe bipolar or unipolar disorder
- A fall or near fall rate < 2/week in average (during a 2-week period between screening and baseline using fall postcards).
- Insufficient fluency in local language to complete neuropsychological, global and gait/balance assessments
- Score < 20 on the mini-mental state examination at screening
Show all 19Show fewer
- Within 4 weeks of screening or during the course of the study concurrent treatment with any cholinesterase inhibitor medication (donepezil, galantamine, rivastigmine) or any cholinergic agent (agonist or antagonist) including memantine.
- History of deep brain stimulation surgery.
- Within 4 weeks of screening or during the course of the study concurrent treatment with beta blockers, any antipsychotic drugs or mood stabilisers.
- Any malignancy within 5 years of screening or current significant - judged as such by the site investigator - hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease.
- Presence of an active gastro-duodenal ulcer, unstable asthma or chronic obstructive pulmonary disease.
- History of or current urinary retention requiring either anticholinergic medication or urethral catheterisation.
- The systolic blood pressure measurement is > 190 or < 85 mm Hg and/or the diastolic blood pressure measurement is > 105 or < 50 mm Hg at screening.
- Clinically significant laboratory abnormalities at screening, including creatinine ≥ 2.5 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times the upper limit of the normal reference range.
- The ECG is abnormal at screening and judged to be clinically significant by the site investigator. Particular attention will be given to any sign suggesting conduction disorders.
- Treatment with any investigational drugs or device within 60 days of screening.
- Ongoing pregnancy or lactation. Women with childbearing potential not using any form of efficacious contraception.
- Any contraindication for rivastigmine as defined by the ANSM
- Known hypersensitivity to rivastigmine or any cholinesterase inhibitor medication.
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Neurologie et Pathologie du Mouvement Hôpital de La Timone
Marseille, 13385
About this study
Official title: RIVA-PSP: Efficacy of Rivastigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy: A Randomised Double Blind Placebo-controlled Clinical Trial
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease from the parkinsonian syndrome group. It represents 5 to 10% of all parkinsonian syndromes and affects 3,000 to 10,000 persons in France. PSP is characterised by a doparesistant parkinsonism with axial signs such as early gait instability and falls, oculomotor signs such as a vertical gaze palsy, dysphagia and dysarthria, and both cognitive and behavioural disturbances. The latter predominantly manifest as psycho-motor slowness, apathy and frontal executive deficits. Swallowing impairments and falls may lead to life-threatening situations and death occurs 6-9 years after disease onset.
Apart from L-dopa which may transiently and inconsistently improve motor symptoms no effective symptomatic, disease-modifying or neuroprotective therapy is presently available to reduce disability in any way. Therefore these patients often receive mostly non-medical care such as physiotherapy and speech therapy.
Read more
In addition to dopaminergic degeneration there is evidence of cholinergic deficits in PSP correlated with gait and balance impairments . This stands in contrast with the limited number of studies of cholinergic augmentation strategies in PSP.
Trials of cholinesterase inhibitors in PSP have produced rather conflicting results: donepezil improves cognition but deteriorates some motor functions whereas a case series of 5 PSP patients treated with rivastigmine found an improvement in several cognitive aspects and no deterioration of motor functions .On the other hand in Parkinson's disease there is convincing evidence of a positive effect of rivastigmine on cognition , apathy and falls Investigators' hypothesis is that rivastigmine (an acetyl- and butyryl-cholinesterase inhibitor) may reduce gait and postural impairment in PSP and may therefore limit the number of falls and their consequences both in terms of injuries sustained (fractures etc...) and on the patients' autonomy. In addition investigators hypothesise that rivastigmine may also reduce the cognitive and behavioural impairment associated with PSP. Taken together these improvements are likely to produce a significant effect on the patients' quality of life and their caregiver burden.
- Conditions
- Progressive Supranuclear Palsy (PSP)
- Being tested
- Rivastigmine, Placebo
- Medical subject headings
- Supranuclear Palsy, Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivastigmineDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Rivastigmine | Active comparator | Subject will receive a treatment of Rivastigmine twice daily during 24 weeks of treatment.
Study drug will be administered orally. Sufficient test drug will be dispensed to subjects or their caregivers at each study visit to allow twice daily dosing until the next scheduled study visit Receives: Drug: Rivastigmine |
| Placebo | Placebo comparator | Subject will receive a placebo twice daily during 24 weeks of treatment. Study drug will be administered orally. Sufficient test drug will be dispensed to subjects or their caregivers at each study visit to allow twice daily dosing until the next scheduled study visit Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy will be assessed at 4 months as the change from baseline of the number of falls and near falls over the past 2 week
Efficacy will be assessed at 4 months as the change from baseline of the number of falls and near falls over the past 2 weeks using fall postcards sent weekly and filled daily by the subject and caregiver. The number of falls and near-falls will be expressed both as the total number of occurrences over that period and as the number of occurrence adjusted to the distance and number of hours walked (assessed using continuous accelerometer recordings)
Measured: baseline, 2 weeks, 4 months
Secondary outcomes (9)
Change from baseline at 4 months measured by the global ans sub scores of the PSPRS scale (Progressive Supranuclear Palsy Rating Scale)
Measured: Baseline and 4 months
Change from baseline at 4 months measured by the Clinical Global Impression scale (patient and caregiver)
Measured: Baseline and 4 months
Apathy assessed using the Lille Apathy Rating Scale (LARS) both subject and caregiver versions
Measured: Baseline and 4 months
Assessment of the Quality of life of patient using the PSP-Quality of Life Scale (PSP-QoL)
Measured: Baseline and 4 months
Assessment of the Quality of life of patient using the EQ-5D
Measured: Baseline and 4 months
Assessment of the Quality of life of the caregiver using the PSP-Quality of Life Scale (PSP-QoL)
Measured: Baseline and 4 months
Assessment of the Quality of life of the caregiver using the EQ-5D
Measured: Baseline and 4 months
Caregiver burden assessed using the Caregiver Reaction Assessement (CRA)
Measured: Baseline and 4 months
Safety: recording of adverse events at each study visit and at the phone calls
Vital signs, laboratory tests and ECGs will be performed at each study visit to monitor any biological or cardiac adverse event
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2016 (estimated)
- Study start26 Jul 2016
- Primary completion3 Jun 2022
- Study completion17 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progressive Supranuclear Palsy (PSP)Studies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine GEINDRE, Study director, Assistance Publique Hôpitaux de Marseille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02839642
- Sponsor's protocol ID
- 2015-11
- Other IDs
- 2016-001319-19, 2016
- Acronym
- RIVA-PSP
- Status last verified
- Jul 2023
- First submitted
- 30 Jun 2016
- Last updated
- 20 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RIVA-PSP: Efficacy of Rivastigmine on Motor, Cognitive and Behavioural Impairment in Progressive Supranuclear Palsy: A Randomised Double Blind Placebo-controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT02839642
- Acronym / sponsor ID
- RIVA-PSP / 2015-11
- Conditions
- Progressive Supranuclear Palsy (PSP)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 26 Jul 2016 (actual)
- Primary completion
- 3 Jun 2022 (actual)
- Study completion
- 17 Nov 2022 (actual)
- First posted
- 21 Jul 2016 (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.
Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease from the parkinsonian syndrome group. It represents 5 to 10% of all parkinsonian syndromes and affects 3,000 to 10,000 persons in France. PSP is characterised by a doparesistant parkinsonism with axial signs such as early gait instability and falls, oculomotor signs such as a vertical gaze palsy, dysphagia and dysarthria, and both cognitive and behavioural disturbances. The latter predominantly manifest as psycho-motor slowness, apathy and frontal executive deficits. Swallowing impairments and falls may lead to life-threatening situations and death occurs 6-9 years after disease onset.
Apart from L-dopa which may transiently and inconsistently improve motor symptoms no effective symptomatic, disease-modifying or neuroprotective therapy is presently available to reduce disability in any way. Therefore these patients often receive mostly non-medical care such as physiotherapy and speech therapy.
In addition to dopaminergic degeneration there is evidence of cholinergic deficits in PSP correlated with gait and balance impairments . This stands in contrast with the limited number of studies of cholinergic augmentation strategies in PSP.
Trials of cholinesterase inhibitors in PSP have produced rather conflicting results: donepezil improves cognition but deteriorates some motor functions whereas a case series of 5 PSP patients treated with rivastigmine found an improvement in several cognitive aspects and no deterioration of motor functions .On the other hand in Parkinson's disease there is convincing evidence of a positive effect of rivastigmine on cognition , apathy and falls Investigators' hypothesis is that rivastigmine (an acetyl- and butyryl-cholinesterase inhibitor) may reduce gait and postural impairment in PSP and may therefore limit the number of falls and their consequences both in terms of injuries sustained (fractures etc...) and on the patients' autonomy. In addition investigators hypothesise that rivastigmine may also reduce the cognitive and behavioural impairment associated with PSP. Taken together these improvements are likely to produce a significant effect on the patients' quality of life and their caregiver burden.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rivastigmine | Active comparator | Drug: RivastigmineSubject will receive a treatment of Rivastigmine twice daily during 24 weeks of treatment. Study drug will be administered orally. Sufficient test drug will be dispensed to subjects or their caregivers at each study visit to allow twice daily dosing until the next scheduled study visit |
| Placebo | Placebo comparator | Drug: PlaceboSubject will receive a placebo twice daily during 24 weeks of treatment. Study drug will be administered orally. Sufficient test drug will be dispensed to subjects or their caregivers at each study visit to allow twice daily dosing until the next scheduled study visit |
Who may qualify
- Ages
- 41 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Probable PSP of the Richardson subtype as defined by the NINDS-SPSP criteria modified so as to allow inclusions of patients who have first fallen within 3 years of disease onset.
- Aged 41 to 80 years at the time of screening
- Judged by site investigator to be able to comply with gait/balance and neuropsychological evaluations at baseline and throughout the study
- Able to ambulate independently or with assistance (cane)
- Score ≥ 20 on the mini-mental state examination (MMSE) at screening
Key exclusion criteria (19 listed)
- Non ambulatory patient.
- History and clinical examination suggesting another parkinsonian syndrome (Parkinson's disease, Dementia with Lewy Bodies, Corticobasal Degeneration, Multisystem Atrophy, Vascular Parkinsonism, tumoral parkinsonism, anti-psychotic drug-induced parkinsonism)
- Presence of other significant neurological or psychiatric disorders: Alzheimer's disease, epilepsy, history of stroke, psychotic disorder, severe bipolar or unipolar disorder
- A fall or near fall rate < 2/week in average (during a 2-week period between screening and baseline using fall postcards).
- Insufficient fluency in local language to complete neuropsychological, global and gait/balance assessments
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 |
|---|---|---|
| Rivastigmine | Drug | Rivastigmine |
| Placebo | Drug | Placebo |
Primary outcome
Efficacy will be assessed at 4 months as the change from baseline of the number of falls and near falls over the past 2 week
Time frame: baseline, 2 weeks, 4 months
Efficacy will be assessed at 4 months as the change from baseline of the number of falls and near falls over the past 2 weeks using fall postcards sent weekly and filled daily by the subject and caregiver. The number of falls and near-falls will be expressed both as the total number of occurrences over that period and as the number of occurrence adjusted to the distance and number of hours walked (assessed using continuous accelerometer recordings)
9 secondary outcomes
Change from baseline at 4 months measured by the global ans sub scores of the PSPRS scale (Progressive Supranuclear Palsy Rating Scale)
Time frame: Baseline and 4 months
Change from baseline at 4 months measured by the Clinical Global Impression scale (patient and caregiver)
Time frame: Baseline and 4 months
Apathy assessed using the Lille Apathy Rating Scale (LARS) both subject and caregiver versions
Time frame: Baseline and 4 months
Assessment of the Quality of life of patient using the PSP-Quality of Life Scale (PSP-QoL)
Time frame: Baseline and 4 months
Assessment of the Quality of life of patient using the EQ-5D
Time frame: Baseline and 4 months
Assessment of the Quality of life of the caregiver using the PSP-Quality of Life Scale (PSP-QoL)
Time frame: Baseline and 4 months
Assessment of the Quality of life of the caregiver using the EQ-5D
Time frame: Baseline and 4 months
Caregiver burden assessed using the Caregiver Reaction Assessement (CRA)
Time frame: Baseline and 4 months
Safety: recording of adverse events at each study visit and at the phone calls
Time frame: 4 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 20 Jul 2023.
- Individual participant dataSharing planned: Undecided
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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.
Catherine GEINDRE study director
Assistance Publique Hôpitaux de Marseille
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 Rivastigmine in people with Progressive Supranuclear Palsy (PSP), run by Assistance Publique Hopitaux De Marseille 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 10 inclusion and 19 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 20 Jul 2023. 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. Some participants in this study may receive a placebo. 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 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?
Efficacy will be assessed at 4 months as the change from baseline of the number of falls and near falls over the past 2 week (time frame: baseline, 2 weeks, 4 months). 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 20 Jul 2023.