Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04002674|
Recruitment Status : Recruiting
First Posted : June 28, 2019
Last Update Posted : April 28, 2021
|Condition or disease||Intervention/treatment||Phase|
|Dementia With Lewy Bodies||Drug: Placebo oral capsule Drug: Nilotinib Oral Capsule||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
Investigators will evaluate the effects of 200 mg of Nilotinib versus matching Placebo taken daily by mouth for 6 Months, followed by 1 Month wash-out period in individuals with DLB.
Sixty (60) participants will be recruited and randomly assigned 1:1 to placebo (arm 1) or 200 mg Nilotinib (arm 2). Participants will be treated for 6 months and monitored every month (4 weeks) in a total of 9 visits that include screening, baseline, 1, 2, 3, 4, 5, 6 months follow up and 7-month washout.
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Participants will be randomized by a Biostatistician by an internet based randomization module into two groups. The researchers include : Primary investigator , Sub-Investigators ,Clinical Coordinators, Nurse Practitioners , and Clinical Reseach unit staff.|
|Official Title:||A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Nilotinib Treatment on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies (DLB)|
|Actual Study Start Date :||January 10, 2020|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||May 31, 2023|
Placebo Comparator: Placebo
Sixty (60) participants will be recruited and randomized into 2 arms (1:1). Thirty (30) patients in arm 1 will receive the matching placebo ("sugar pill") one (1) capsule orally (without food) once daily for 6 months (180 days).
Drug: Placebo oral capsule
Thirty (30) patients in arm 1 will receive the matching placebo ("sugar pill") one (1) capsule orally (without food) once daily for 6 months (180 days).
Other Name: Placebo
Active Comparator: 200 mg Nilotinib
Sixty (60) participants will be recruited and randomized into 2 arms (1:1). Thirty (30) patients in arm 2 will receive the 200 mg of Nilotinib one (1) capsule orally (without food) once daily for 6 months (180 days).
Drug: Nilotinib Oral Capsule
Thirty (30) patients in arm 2 will receive the 200 mg of Nilotinib one (1) capsule orally (without food) once daily for 6 months (180 days).
Other Name: Tasigna
- Safety and tolerability: occurrence of adverse events (AEs) [ Time Frame: 6 Months ]The Investigators will determine safety and tolerability using the occurrence of adverse events (AEs) of interest as per Nilotinib Investigator Brochure (IB).
- The Investigator will determine Nilotinib levels in CSF and plasma. [ Time Frame: 6 Months ]Pharmacokinetics: Measure the CSF concentration of Nilotinib
- The Investigators will determine changes in DLB related CSF and plasma biomarkers [ Time Frame: 6 Months ]Pharmacodynamics: Determine the effects of Nilotinib on primary biomarkers, including changes of CSF levels of HVA between baseline and 6 months.Furthermore, measure the CSF concentration of surrogate/exploratory biomarkers.
- The investigators will quantify amyloid burden via Florbetaben PET scan [ Time Frame: 6 Months ]Quantification of brain amyloid burden via Florbetaben PET at baseline and 6 months (end of treatment)
- Measurement of the effects of Nilotinib on Cognition using the Montreal Cognitive Assessment (MoCA) [ Time Frame: 6 Months ]The MoCA is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains, including attention and concentration, executive functions, memory, language, visuo-constructional skills, conceptual thinking, calculations and orientation. Scores range between 0 and 30 where 30 is the highest score and 0 is the lowest score.
- Measurement of the effects of Nilotinib on Cognition using the Trail Making Test (TMT) [ Time Frame: 6 Months ]The Trail Making Test (TMT) is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning. The time to complete the test is measured in seconds.
- Measuring the effects of NIlotinib on Cognition using the Alzheimer's Disease Assessment Scale - cognitive (ADAS-cog). [ Time Frame: 6 Months ]ADAS-cog aims to evaluate cognitive impairment in Alzheimer's disease. ADAS-cog was included in this LBD study to better capture potential changes in activities of daily living (ADL) and non-ADLs and severity of cognitive impairment. Points for errors in each task are added up and the greater the dysfunction, the greater the total score. The lower the dysfunction the lower the total score .
- Measuring the effects of Nilotinib on Behavior using the Alzheimer's disease Cooperative Study-Activity of Daily Living scale [ Time Frame: 6 Months ]ADCS-ADL is an activity of daily living inventory to assess functional performance. Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the prior 4 weeks and their level of performance. The ADCS-ADL includes some items from traditional basic ADL tests as well as instrumental (complex) activities of daily living. It is a 23 item scale that provide a total score from 0-78 with a lower score indicating greater severity.
- Measuring the effects of Nilotinib on Behavior using the Neuropsychiatric Inventory (NPI) [ Time Frame: 6 Months ]The NPI is a multi-item instrument to assess psychopathology in Azheimer's disease based on interview with the study partner. 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 and the score for each subscale are the product of severity and frequency.
- Measuring the effects of Nilotinib on Behavior using the Clinical Assessment of Fluctuation (CAF) [ Time Frame: 6 Months ]The CAF consists of seven items of confusional behavior (falls, fluctuation, drowsiness, attention, disorganized thinking, altered level of consciousness, communication), scores for which are summed to provide a severity score for fluctuating confusion ranging from 0 to 21
- Measuring the effects of Nilotinib on Behavior using the Irritability-Apathy Scale (IAS) [ Time Frame: 6 Months ]The IAS measures apathy and irritability in patients with dementia. The IAS is a 28-item self-administered questionnaire collecting information about different aspects of irritability and apathy utilizing a 0-3 scale for each item to indicate severity. Both a patient and a study partner version can be administered. The IAS will be completed separately by Subjects and Study Partners. A higher total score indicates higher severity , a lower one indicated lower severity.
- Measuring the effects of Nilotinib on Behavior using the Problem Behaviors Assessment short form (PBA-s) [ Time Frame: 6 Months ]PBA-s is a structured interview in which a trained interviewer rates the frequency and severity of neuropsychiatric symptoms through observation and the reporting of the Subject and Study Partner. Symptoms rated include depressed mood, suicidal ideation, anxiety, irritability, angry or aggressive behavior, apathy, perseverative thinking or behavior, obsessive-compulsive behaviors, delusional or paranoid thinking, hallucinations, and disoriented behavior. Each behavioral problem is rated for both severity and frequency on a 0-4- point scale; severity and frequency ratings are then multiplied to provide an overall score for each symptom.
- Measuring the effects of Nilotinib on Motor Function by using the Unified Parkinson's Disease Rating Scale (UPDRS)-I-III. [ Time Frame: 6 Months ]UPDRS-I-III is used to follow the longitudinal course of Parkinson's disease. The UPDRS is made up of these sections: Part I: evaluation of mentation, behavior, and mood. Part II: self-evaluation of the activities of daily life (ADLs) Part III: clinician-scored monitored motor evaluation. Part IV: complications of therapy. Part V: Hoehn and Yahr staging of severity of Parkinson's disease. Part VI: Schwab and England ADL scale. The greater the score the higher the severity, the lower the score the lower the severity. The maximum possible UPDRS score is 199.
- Measuring the effects of Nilotinib on Motor Function by using the Timed-Up-And-Go (TUG). [ Time Frame: 6 Months ]Timed Up and Go (TUG) is an assessment of mobility, balance, walking ability, and fall risk. It measures the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down. This assessment is measured in seconds.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04002674
|Contact: Myrna J Arellano, RN||(202)-email@example.com|
|Contact: Sara Matar, BSfirstname.lastname@example.org|
|United States, District of Columbia|
|MedStar Georgetown University Hospital||Recruiting|
|Washington, District of Columbia, United States, 20007|
|Contact: Fernando Pagan, MD 202-444-1382 email@example.com|
|Contact: Sara Matar, BS 202-687-7581 firstname.lastname@example.org|
|Principal Investigator: Fernando L Pagan, MD|
|Sub-Investigator: Charbel E Moussa, MD,PhD|
|Principal Investigator:||Fernando L Pagan, MD||Georgetown University|