Alzheimer's DiseasePhase 2R2NCT02359552
Rasagiline Rescue in Alzheimer's Disease Clinical Trial
A Phase 2 study testing Rasagiline in people with Alzheimer's Disease, run by The Cleveland Clinic at 3 sites in United States.
Trial summary
This is a Phase II, randomized, double blind, placebo controlled, parallel group, proof of concept three-site study, to evaluate the effect of Rasagiline in the regional brain metabolism on 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG-PET). Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Rasagiline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2015to 4 Jan 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females 50 to 90 of age inclusive.
- Diagnosis of probable AD (NINCDS-ADRDA criteria)
- Positive fluoro-deoxyglucose PET ([18F]-FDG PET) scan compatible with AD as determined by the ADM Diagnostics LLC (ADMdx) Criteria at screening
- Mini Mental Status Exam = 12 - 22 (inclusive)
- Must have a study partner who is able and willing to comply with all required study procedures.
- Have at least eight years of education and should have previously (in pre-AD condition) been capable of reading, writing, and communicating effectively with others in English.
- If receiving therapy with a cholinesterase inhibitor and/or memantine, the dose of these agents has been stable for at least 3 months prior to screening
Who cannot join
- Any non-AD neurological disease
- MRI findings indication of a non-AD diagnosis
- Screening laboratory studies that are 1.5 times above or below the highest and lowest range of normal for each test respectively
- History of melanoma; history of malignancy within the past five years with the exception of basal cell or squamous cell cancer, in-situ cervical cancer, or localized prostate cancer
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
Cleveland Clinic Lakewood Hospital
Lakewood, Ohio, 44107
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106
About this study
Official title: A 24-week, Three-site, Randomized, Double Blind, Placebo Controlled, Parallel Group, Proof-of-concept Study to Evaluate Rasagiline in the Regional Brain Metabolism on FDG PET in Patients With Mild to Moderate Alzheimer's Disease
This is a Phase II, randomized, double blind, placebo controlled, parallel group, proof of concept three-site study, to evaluate the effect of Rasagiline in the regional brain metabolism on 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG-PET).
Read the detailed description
The study consists of two phases: a 24 week double blind placebo controlled treatment period and a 4 week follow up period. Patients will be randomized in a 1: 1 ratio at baseline to receive either Rasagiline or matching placebo
The study drug will be given as 0.5 mg dose once daily for the 4 weeks, then increases to 1 mg daily for the next 20 weeks. A total of 50 subjects will be enrolled: 25 will receive Rasagiline and 25 will receive matching placebo for the 24-week treatment period.
Primary objective is to determine if exposure to 1 mg of Rasagiline daily is associated with improved regional brain metabolism in the treatment group compared to the placebo group in Alzheimer's Disease patients
- Conditions
- Alzheimer's Disease
- Being tested
- Rasagiline, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RasagilineDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment.
Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Receives: Drug: Placebo |
| Rasagiline | Active comparator | Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment.
Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Receives: Drug: Rasagiline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Regional Glucose Metabolism Between Week 24 and Baseline as Measured by 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (FDG-PET).
The primary outcome measure is the change from baseline to week 24 in FDG-PET as measured by Standard Uptake Units Regional (SUVR) in several pre-specified brain regions including the medial temporal, lateral temporal, posterior cingulate - precuneus, inferior parietal, middle frontal, anterior cingulate, and striatum. The SUVR change was calculated by subtracting the value at 24 weeks from baseline values. Negative values indicate increased hypometabolism (i.e. worsening of cell function).
Measured: 24 weeks
Secondary outcomes (7)
Change in ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) Score
The ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 70 (worse). We used total ADAS-Cog 11 scores, which is a sum of individual subscales. We calculated the change by subtracting the ADAS Cog score at week 24 from baseline score. A positive change indicates cognitive worsening.
Measured: Mean change in scores from baseline to week 24
Change in MMSE (Mini Mental Status Examination) Score
Measure Description: The MMSE (Mini Mental Status Examination) is a brief, frequently used screening instrument for AD drug studies. The MMSE evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. A lower score indicates more cognitive impairment. The highest score is 30, range is between 0 (severe impairment) and 30 (cognitively normal). We calculated the change in scores by subtracting week 24 score from baseline. A negative score indicates clinical worsening.
Measured: Mean change in scores from baseline to week 24
Change in ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) Score
Measure Description: The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is an activities-of-daily-living inventory developed by the ADCS to assess functional performance in participants with AD. Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the past 4 weeks and their level of performance. The ADCS-ADL provides a total score from 0-78, with a lower score indicating greater severity. We calculated change by subtracting scores on week 24 test from the baseline score. A negative score indicates worsening ability to complete ADLs.
Measured: Mean change in scores from baseline to week 24
Change in NPI (Neuropsychiatric Inventory) Score
Measure Description: The behavioral outcome measure for this trial is the NPI (Neuropsychiatric Inventory). The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score is calculated by summing the severity and frequency of the subscale measures. The range of scores is 0-40. A score of 0 indicates no behavioral impairment and a score of 40 indicates severe behavioral impairment. We calculated change by subtracting Week 24 scores from baseline scores. A positive change indicates behavioral worsening.
Measured: Mean change in scores from baseline to week 24
Change in Digit Span
Measure Description: The Digit Span consists of repetition of increasing long strings of digits presented at 1 per second as read by the examiner and repeated by the subject.The score is the maximum number of digits the patient can repeat until they fail twice in a row. The reverse digit span is identical to the forward digit span except that the patient repeats the presented digits in reverse order. The score is the maximum number of digits the patient can repeat in reverse order until they fail twice in a row. Each correct response is worth one point with a maximum total score of 28. A higher score is better. We calculated change by subtracting week 24 score from baseline score. A negative score indicates worse performance over the course of study.
Measured: Mean change in scores from baseline to week 24
Change in COWAT (Controlled Oral Word Association Test) Score
Measure Description: Study participants are instructed, "I want to see how many words you can say beginning with a certain letter in one minute." The study participant's responses are recorded on the worksheet. Study participants are then given an additional one minute for each of two different letters using similar instructions. The score is the total number of acceptable words for the three trials combined. A higher score represents better performance.
Responses are then judged for their acceptability (example for the use of proper nouns, numbers, repetitions and stem word with a different ending). The score is the total number of acceptable words for the three trials combined. A higher score represents better performance. We calculated change by subtracting week 24 scores from baseline scores. A negative score indicates worse performance.
Measured: Mean change in scores from baseline to week 24
Change in QoL-AD (Quality of Life - Alzheimer's Disease) Score
Measure Description: The QoL-AD (Quality of Life - Alzheimer's Disease) is a commonly used 13 item QoL scale that assesses items specific to QoL in patients with cognitive impairment. It is administered to the research partner with answers for the patient. Points are assigned to each item as follows: poor = 1, fair = 2, good = 3, excellent = 4.The total score is the sum of all 13 items. The range of score is from 0-52. We calculated the change by subtracting the scores on week 24 score from baseline. A negative value indicates worsening quality of life.
Measured: This assessment will be performed at the Baseline and Week 24 visits.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study startMay 2015
- Primary completion29 Aug 2018
- Study completion4 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey L Cummings, MD, ScD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02359552
- Sponsor's protocol ID
- 14-519
- Acronym
- R2
- Status last verified
- Oct 2020
- First submitted
- 5 Feb 2015
- Last updated
- 10 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984 Nov;141(11):1356-64. doi: 10.1176/ajp.141.11.1356.
PubMed 6496779Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
PubMed 1202204Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9.
PubMed 9236950Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997 May;48(5 Suppl 6):S10-6. doi: 10.1212/wnl.48.5_suppl_6.10s.
PubMed 9153155
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24-week, Three-site, Randomized, Double Blind, Placebo Controlled, Parallel Group, Proof-of-concept Study to Evaluate Rasagiline in the Regional Brain Metabolism on FDG PET in Patients With Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT02359552
- Acronym / sponsor ID
- R2 / 14-519
- Conditions
- Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- May 2015 (actual)
- Primary completion
- 29 Aug 2018 (actual)
- Study completion
- 4 Jan 2019 (actual)
- First posted
- 10 Feb 2015 (estimated)
- Results
- Posted 20 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase II, randomized, double blind, placebo controlled, parallel group, proof of concept three-site study, to evaluate the effect of Rasagiline in the regional brain metabolism on 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG-PET).
Detailed description
The study consists of two phases: a 24 week double blind placebo controlled treatment period and a 4 week follow up period. Patients will be randomized in a 1: 1 ratio at baseline to receive either Rasagiline or matching placebo
The study drug will be given as 0.5 mg dose once daily for the 4 weeks, then increases to 1 mg daily for the next 20 weeks. A total of 50 subjects will be enrolled: 25 will receive Rasagiline and 25 will receive matching placebo for the 24-week treatment period.
Primary objective is to determine if exposure to 1 mg of Rasagiline daily is associated with improved regional brain metabolism in the treatment group compared to the placebo group in Alzheimer's Disease patients
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). |
| Rasagiline | Active comparator | Drug: RasagilineSubjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males or females 50 to 90 of age inclusive.
- Diagnosis of probable AD (NINCDS-ADRDA criteria)
- Positive fluoro-deoxyglucose PET ([18F]-FDG PET) scan compatible with AD as determined by the ADM Diagnostics LLC (ADMdx) Criteria at screening
- Mini Mental Status Exam = 12 - 22 (inclusive)
- Must have a study partner who is able and willing to comply with all required study procedures.
Key exclusion criteria (4 listed)
- Any non-AD neurological disease
- MRI findings indication of a non-AD diagnosis
- Screening laboratory studies that are 1.5 times above or below the highest and lowest range of normal for each test respectively
- History of melanoma; history of malignancy within the past five years with the exception of basal cell or squamous cell cancer, in-situ cervical cancer, or localized prostate cancer
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 |
|---|---|---|
| Rasagiline | Drug | Rasagiline |
| Placebo | Drug | Placebo |
Primary outcome
Change in Regional Glucose Metabolism Between Week 24 and Baseline as Measured by 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (FDG-PET).
Time frame: 24 weeks
The primary outcome measure is the change from baseline to week 24 in FDG-PET as measured by Standard Uptake Units Regional (SUVR) in several pre-specified brain regions including the medial temporal, lateral temporal, posterior cingulate - precuneus, inferior parietal, middle frontal, anterior cingulate, and striatum. The SUVR change was calculated by subtracting the value at 24 weeks from baseline values. Negative values indicate increased hypometabolism (i.e. worsening of cell function).
7 secondary outcomes
Change in ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) Score
Time frame: Mean change in scores from baseline to week 24
Change in MMSE (Mini Mental Status Examination) Score
Time frame: Mean change in scores from baseline to week 24
Change in ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) Score
Time frame: Mean change in scores from baseline to week 24
Change in NPI (Neuropsychiatric Inventory) Score
Time frame: Mean change in scores from baseline to week 24
Change in Digit Span
Time frame: Mean change in scores from baseline to week 24
Change in COWAT (Controlled Oral Word Association Test) Score
Time frame: Mean change in scores from baseline to week 24
Change in QoL-AD (Quality of Life - Alzheimer's Disease) Score
Time frame: This assessment will be performed at the Baseline and Week 24 visits.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 6496779Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984 Nov;141(11):1356-64. doi: 10.1176/ajp.141.11.1356.
- Background: PubMed 1202204Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98. doi: 10.1016/0022-3956(75)90026-6. No abstract available.
- Background: PubMed 9236950Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9.
- Background: PubMed 9153155Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997 May;48(5 Suppl 6):S10-6. doi: 10.1212/wnl.48.5_suppl_6.10s.
- Individual participant dataSharing planned: No
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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.
Jeffrey L Cummings, MD, ScD principal investigator
The Cleveland Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rasagiline in people with Alzheimer's Disease, run by The Cleveland Clinic at 3 sites in United States.
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 7 inclusion and 4 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 10 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Regional Glucose Metabolism Between Week 24 and Baseline as Measured by 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (FDG-PET). (time frame: 24 weeks). 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 NCT02359552, 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 10 Nov 2020.