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CompletedNCT04002674Updated Jun 12, 2026Results posted

Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies

A Phase 2 interventional study of Placebo oral capsule and Nilotinib Oral Capsule in Dementia With Lewy Bodies, sponsored by Georgetown University. Completed at 1 site in United States. Open to participants aged 25 Years to 90 Years. Per ClinicalTrials.gov, last updated 2026-06-12.

Sponsored by Georgetown University · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
43
Allocation
Randomized
Ages
25 Years to 90 Years
Sex
All
01

Study summary

Dementia with Lewy Bodies (DLB) is an alphasynucleinopathy and the second most common form of dementia in the elderly. DLB shares striking neuropathological and clinical similarities with both Parkinson's disease (PD) and Alzheimer's disease (AD). Nilotinib (Tasigna®, AMN107, Novartis, Switzerland) is approved by the FDA and is well tolerated for CML treatment at oral doses of 600-800mg daily. The Investigators propose to perform a phase II randomized, double blinded, placebo controlled study to evaluate the impact of Nilotinib in patients with DLB.

Read the detailed description

A phase II randomized, double blinded, placebo controlled study will be performed to evaluate the impact of Nilotinib (Tasigna®, AMN107, Novartis, Switzerland) on safety, tolerability, pharmacokinetics, pharmacodynamics and clinical outcomes in patients with Dementia with Lewy Bodies. Sixty ( 60) participants will be recruited and randomly assigned 1:1 to placebo (arm 1) or 200 mg Nilotinib (arm 2).This study will be conducted in DLB patients with 2.5≥Hoehn \& Yahr≤3 and UPDRS I-III ≤50 and 15≥UPDRS III (motor) ≥40 (Unified Parkinson's Disease Rating Score)and MoCA≥18(Montreal Cognitive Assessment). Eligible participants must be stable on MAO-B inhibitors (Rasageline or Selegeline) for 4 weeks and must not be on ≥800mg Levodopa daily. Participants must be stable on acetylcholinesterase inhibitors and other medications for at least 6 weeks. 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. Blood and cerebrospinal fluid (CSF) will be collected at baseline and at 6 months to determine Nilotinib effects on CSF biomarkers.

02

Conditions studied

  • Dementia With Lewy Bodies

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03

In context

Lewy Body Disease

231 studies on the registry are indexed under Lewy Body Disease; 89 are open to participants now.

This study's enrollment of 43 is below the median of 83 across 142 interventional studies indexed under Lewy Body Disease.

Browse Lewy Body Disease studies →

Lead sponsor

Georgetown University is the lead sponsor of 286 studies on the registry; 42 are open to participants now.

Of its 28 completed or terminated interventional studies of FDA-regulated products, 20 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
25 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Written informed consent
  2. Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR).
  3. Clinical diagnosis of DLB according to McKeith et al (7) with both dementia MoCA≥18 and Parkinsonian defined as bradykinesia in combination with rest tremor, rigidity or both UPDRS I-III is less than 50 and/or UPDRS-III between 15 -40 on-state. Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
  4. 2.5 ≥Hoehn and Yahr stage ≤3
  5. MDS-UPDRS-III 15-40 on-state (or up to 70 on the off state)
  6. Abnormal DaTScan
  7. Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
  8. Patients between the age of 25-90 years, medically stable
  9. Must NOT be stable on mono-amine oxidase (MAO)-B inhibitors (Selegeline or rasagiline) for at least 4 weeks before enrollment and during Nilotinib treatment.
  10. Must be medically stable on less than or equal to 800mg Levodopa daily for at least 4 weeks
  11. QTc interval 350-460 ms, inclusive
  12. Participants must be willing to undergo LP at baseline and 6 months after treatment

Exclusion criteria

Exclusion Criteria:

  1. Patients with hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥461 ms
  2. Concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infraction or cardiac failure, angina, arrhythmia

  3. History or presence of cardiac conditions including:

    1. Cardiovascular or cerebrovascular event (e.g. myocardial infarction, unstable angina, or stroke)
    2. Congestive heart failure
    3. First, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances
    4. Any history of Torsade de Pointes

  4. Treatment with any of the following drugs at the time of screening or the preceding 30 days, and/or planned use over the course of the trial:

    1. Treatment with Class IA or III antiarrhythmic drugs (e.g. quinidine)
    2. Treatment with QT prolonging drugs (www.crediblemeds.org)- excluding Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g. Citalopram, Paxil, Zoloft, Cymbalta, Sertraline, etc...)
    3. Strong CYP3A4 inhibitors (including grapefruit juice). The concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) must be avoided. Grapefruit products may also increase serum concentrations of Nilotinib. Should treatment with any of these agents be required, therapy with Nilotinib should be interrupted.
    4. Anticoagulants, including Coumadin (warfarin), heparin, enoxaparin, daltiparin, xarelto, etc.
    5. St. John's Wort and the concomitant use of strong other CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) must be avoided since these agents may reduce the concentration of Nilotinib.
  5. Abnormal liver function defined as AST and/or ALT > 100% the upper limit of the normal
  6. Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal
  7. History of HIV, clinically significant chronic hepatitis, or other active infection
  8. Females must not be lactating, pregnant or with possible pregnancy
  9. Medical history of liver or pancreatic disease
  10. Clinical signs indicating syndromes other than DLB, including, PD, PD with Dementia (PDD), corticobasal degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic encephalopathy, signs of frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, Babinski sign
  11. Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
  12. Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory abnormality
  13. Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history of skin melanoma or stable prostate cancer are not exclusionary)
  14. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets \< 100,000, use of Coumadin/warfarin, or history of a bleeding disorder
  15. Must not be on any immunosuppressant medications or IVIG
  16. Must not be enrolled as an active participant in another clinical study
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
43 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugPlacebo 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).

    Also known as: Placebo

  • DrugNilotinib 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).

    Also known as: Tasigna

06

What researchers measure

Primary outcomes

  1. Safety and Tolerability: Occurrence of Adverse Events (AEs)

    The Investigators will determine safety and tolerability using the occurrence of adverse events (AEs) of interest as per Nilotinib Investigator Brochure (IB).

    Time frame: 6 Months

Secondary outcomes

  1. DLB Related CSF Biomarkers

    Pharmacodynamics: Determine the effects of Nilotinib on primary biomarkers

    Time frame: 6 Months

  2. The Investigators Will Quantify Amyloid Burden Via Florbetaben PET Scan

    Quantification of Standardized Uptake Value Ratio (SUVR) of brain amyloid burden via Florbetaben (Neuraceq, is a diagnostic radiotracera) PET at baseline and 6 months (end of treatment (EOT)). Standardized Uptake Value Ratio (SUVR) is a unitless ratio that measures tracer uptake in a target brain region compared to a reference region. A lower SUVR is generally better in amyloid PET scans, as it indicates a lower density of amyloid plaques in the brain while a higher SUVR indicates a higher burden of amyloid plaque accumulation in the brain.

    Time frame: Baseline, 6 Months, and change between baseline and 6 months

  3. DLB Related CSF Biomarkers

    Pharmacodynamics: Determine the effects of Nilotinib on CSF levels of Homavanillic Acid (HVA) between baseline and 6 months.

    Time frame: Changes from Baseline to 6 months

  4. DLB Related CSF Biomarkers

    Pharmacodynamics: Determine the effects of Nilotinib on the ratio change of phospho-Tau(181)/Abeta42 (pTau(181)/Ab42) in DLB patients

    Time frame: 6 months

Other outcomes

  1. Measure the Effects of Nilotinib on Cognition Using the Montreal Cognitive Assessment (MoCA)

    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; a score of 26 or higher is generally considered normal, while lower scores indicate impairment.

    Time frame: Change from Baseline in the Montreal Cognitive Assessment at 6 months

  2. Measure the Effects of Nilotinib on Cognition Using the Trail Making Test (TMT)

    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. Lower times indicate better executive function, while higher scores suggest impairment.

    Time frame: Change from Baseline in the Trail Making Test at 6 months

  3. Measure the Effects of NIlotinib on Cognition Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog14).

    The 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog14) measures cognitive impairment, with higher scores (0-90) indicating greater disability.

    Time frame: Change from Baseline in the Alzheimer's Disease Assessment Scale - cognitive at 6 months

  4. Measure the Effects of Nilotinib on Behavior Using the Alzheimer's Disease Cooperative Study-Activity of Daily Living Scale (ADCS-ADL)

    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.

    Time frame: Change from Baseline in the Alzheimer's Disease Cooperative Study-Activity of Daily Living Scale at 6 months

  5. Measure the Effects of Nilotinib on Behavior Using the Neuropsychiatric Inventory (NPI)

    The Neuropsychiatric Inventory (NPI) is a test widely used, clinician-administered tool that evaluates 12 behavioral domains in dementia patients (e.g., agitation, depression, delusions). Each item is scored by multiplying frequency (1-4) by severity (1-3), resulting in a maximum total score of 144, with higher scores indicating greater neuropsychiatric symptoms, often aligning with disease progression. Minimum Score is 0 (no behavioral symptoms present); maximum Score is 144 (highest severity and frequency across all 12 domains). Higher scores indicate a higher frequency and greater severity of neuropsychiatric symptoms (such as delusions, agitation, or apathy) while lower scores indicate few or no behavioral and psychiatric symptoms.

    Time frame: Change from Baseline in Neuropsychiatric Inventory at 6 months

  6. Measure the Effects of Nilotinib on Behavior Using the Clinical Assessment of Fluctuation (CAF)

    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. Higher scores indicate more severe fluctuations while lower scores indicate less severe fluctuations.

    Time frame: Change from Baseline in Clinical Assessment of Fluctuation at 6 months

  7. Measure the Effects of Nilotinib on Behavior Using the Irritability-Apathy Scale (IAS)

    The IAS measures apathy and irritability in patients with dementia. The IAS is a 14-item self-administered questionnaire collecting information about different aspects of irritability and apathy utilizing a 0-3 scale for each item to indicate severity (0 (absent) to 3 (maximum intensity) per question). Total Range is 0-42; a higher total score indicates more severe symptoms, which are often associated with greater morbidity and worse functional outcomes while a lower score indicates lower severity.

    Time frame: Change from Baseline in Irritability-Apathy Scale at 6 months

  8. Measure the Effects of Nilotinib on Behavior Using the Problem Behaviors Assessment Short Form (PBA-s)

    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. Minimum score is 0 (symptom is absent); maximum score is 176 (11 items × maximum severity 4 × maximum frequency 4). Higher scores indicate increased frequency or severity of behavioral issues while lower scores indicate decreased severity and frequency.

    Time frame: Change from Baseline in Problem Behaviors Assessment short form at 6 months

  9. Measure the Effects of Nilotinib on Motor Function by Using the Unified Parkinson's Disease Rating Scale (UPDRS)-I-III.

    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. The minimum possible score on the UPDRS is 0, which indicates no disability or no symptoms of Parkinson's disease. The scale, used to assess severity, typically ranges from 0 to 199 (total) (199 being the maximum) or 0 to 108 (motor section, Part III) (108 being maximum). Higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-III indicate increased severity of disease, greater disability, and more significant impairment, while lower scores signify better function.

    Time frame: Change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS)-I-III at 6 months

  10. Measure the Effects of Nilotinib on Motor Function by Using the Timed-Up-And-Go (TUG).

    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. A score of less than 10 seconds is normal, 14-20 seconds indicates a high fall risk or frailty, and over 30 seconds suggests significant mobility impairment.

    Time frame: Change from Baseline in Timed-Up-And-Go at 6 months

07

Results

Posted Apr 3, 2026

Participant flow

Participant flow — Overall Study
MilestonePlacebo200 mg Nilotinib
Started2221
Completed1819
Not completed42

Outcome measures

PrimarySafety and Tolerability: Occurrence of Adverse Events (AEs)

The Investigators will determine safety and tolerability using the occurrence of adverse events (AEs) of interest as per Nilotinib Investigator Brochure (IB).

Time frame:
6 Months
Reported as:
Number · events
Safety and Tolerability: Occurrence of Adverse Events (AEs)
eventsPlacebo200 mg Nilotinib
Severe Adverse Events22
Adverse Events7437
Falls216
SecondaryDLB Related CSF Biomarkers

Pharmacodynamics: Determine the effects of Nilotinib on primary biomarkers

Time frame:
6 Months
Reported as:
Mean · pg/ml
DLB Related CSF Biomarkers
pg/mlPlacebo200 mg Nilotinib
Amyloid beta-42234.1 ± 72.15358.6 ± 183.9
phospho-Tau (181)74.89 ± 44.8548.13 ± 22.64
Total alpha synuclein1685 ± 988.51269 ± 498.6
Matrix metalloprotease-1029.41 ± 17.2619.21 ± 8.848
SecondaryThe Investigators Will Quantify Amyloid Burden Via Florbetaben PET Scan

Quantification of Standardized Uptake Value Ratio (SUVR) of brain amyloid burden via Florbetaben (Neuraceq, is a diagnostic radiotracera) PET at baseline and 6 months (end of treatment (EOT)). Standardized Uptake Value Ratio (SUVR) is a unitless ratio that measures tracer uptake in a target brain region compared to a reference region. A lower SUVR is generally better in amyloid PET scans, as it indicates a lower density of amyloid plaques in the brain while a higher SUVR indicates a higher burden of amyloid plaque accumulation in the brain.

Time frame:
Baseline, 6 Months, and change between baseline and 6 months
Reported as:
Mean · unitless ratio
The Investigators Will Quantify Amyloid Burden Via Florbetaben PET Scan
unitless ratioPlacebo200 mg Nilotinib
Baseline: Frontal Cortex3.46 ± 0.83.16 ± 0.79
6 months: Frontal Cortex3.5 ± 0.83.03 ± 0.84
Change from Baseline: Frontal Cortex0.04 ± 0.2-0.13 ± 0.59
Baseline: Temporal Lobe3.0 ± 0.753.16 ± 0.7
6 months: Temporal Lobe3.02 ± 0.783.07 ± 0.76
Change from Baseline: Temporal Lobe0.02 ± 0.19-0.09 ± 0.57
SecondaryDLB Related CSF Biomarkers

Pharmacodynamics: Determine the effects of Nilotinib on CSF levels of Homavanillic Acid (HVA) between baseline and 6 months.

Time frame:
Changes from Baseline to 6 months
Reported as:
Mean · nM
DLB Related CSF Biomarkers
nMPlacebo200 mg Nilotinib
Change from Baseline-40.90 ± 68.357.64 ± 109.2
Baseline224.6 ± 149.2277.1 ± 264.9
End of Treatment (EOT)183.7 ± 105334.8 ± 285.3
SecondaryDLB Related CSF Biomarkers

Pharmacodynamics: Determine the effects of Nilotinib on the ratio change of phospho-Tau(181)/Abeta42 (pTau(181)/Ab42) in DLB patients

Time frame:
6 months
Reported as:
Mean · ratio
DLB Related CSF Biomarkers
ratioPlacebo200 mg Nilotinib
DLB Related CSF Biomarkers0.3081 ± 0.22480.1764 ± 0.1254
Other pre-specifiedMeasure the Effects of Nilotinib on Cognition Using the Montreal Cognitive Assessment (MoCA)

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; a score of 26 or higher is generally considered normal, while lower scores indicate impairment.

Time frame:
Change from Baseline in the Montreal Cognitive Assessment at 6 months
Reported as:
Mean · points on a scale
Measure the Effects of Nilotinib on Cognition Using the Montreal Cognitive Assessment (MoCA)
points on a scalePlacebo200 mg Nilotinib
MOCA-1.37 ± 3.020.11 ± 1.71
MOCA (Baseline)23.68 ± 5.2625.26 ± 3.33
MOCA (6mths)22.32 ± 5.6825.44 ± 3.94
Other pre-specifiedMeasure the Effects of Nilotinib on Cognition Using the Trail Making Test (TMT)

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. Lower times indicate better executive function, while higher scores suggest impairment.

Time frame:
Change from Baseline in the Trail Making Test at 6 months
Reported as:
Mean · seconds
Measure the Effects of Nilotinib on Cognition Using the Trail Making Test (TMT)
secondsPlacebo200 mg Nilotinib
TMT12.60 ± 33.36-2.44 ± 72.87
TMT (Baseline)213.63 ± 88.96196.68 ± 79.10
TMT (6 mths)227.67 ± 90.85200.94 ± 74.38
Other pre-specifiedMeasure the Effects of NIlotinib on Cognition Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog14).

The 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog14) measures cognitive impairment, with higher scores (0-90) indicating greater disability.

Time frame:
Change from Baseline in the Alzheimer's Disease Assessment Scale - cognitive at 6 months
Reported as:
Mean · score on a scale
Measure the Effects of NIlotinib on Cognition Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog14).
score on a scalePlacebo200 mg Nilotinib
ADAS-Cog2.46 ± 6.12-0.70 ± 5.36
ADAS-Cog (Baseline)25.88 ± 10.7624.20 ± 10.98
ADAS-Cog (6mths)28.33 ± 12.6023.50 ± 13.08
Other pre-specifiedMeasure the Effects of Nilotinib on Behavior Using the Alzheimer's Disease Cooperative Study-Activity of Daily Living Scale (ADCS-ADL)

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.

Time frame:
Change from Baseline in the Alzheimer's Disease Cooperative Study-Activity of Daily Living Scale at 6 months
Reported as:
Mean · points on a scale
Measure the Effects of Nilotinib on Behavior Using the Alzheimer's Disease Cooperative Study-Activity of Daily Living Scale (ADCS-ADL)
points on a scalePlacebo200 mg Nilotinib
ADCS-ADL-4.47 ± 8-1.22 ± 3.61
ADCS-ADL (Baseline)65.72 ± 13.4772 ± 6.7
ADCS-ADL (6mths)61.25 ± 15.770.78 ± 7.64
Other pre-specifiedMeasure the Effects of Nilotinib on Behavior Using the Neuropsychiatric Inventory (NPI)

The Neuropsychiatric Inventory (NPI) is a test widely used, clinician-administered tool that evaluates 12 behavioral domains in dementia patients (e.g., agitation, depression, delusions). Each item is scored by multiplying frequency (1-4) by severity (1-3), resulting in a maximum total score of 144, with higher scores indicating greater neuropsychiatric symptoms, often aligning with disease progression. Minimum Score is 0 (no behavioral symptoms present); maximum Score is 144 (highest severity and frequency across all 12 domains). Higher scores indicate a higher frequency and greater severity of neuropsychiatric symptoms (such as delusions, agitation, or apathy) while lower scores indicate few or no behavioral and psychiatric symptoms.

Time frame:
Change from Baseline in Neuropsychiatric Inventory at 6 months
Reported as:
Mean · score on a scale
Measure the Effects of Nilotinib on Behavior Using the Neuropsychiatric Inventory (NPI)
score on a scalePlacebo200 mg Nilotinib
NPI3.37 ± 12.130.17 ± 7.33
NPI (Baseline)13.86 ± 15.3811.10 ± 8.65
NPI (6mths)18.32 ± 17.8510.89 ± 9.16
Other pre-specifiedMeasure the Effects of Nilotinib on Behavior Using the Clinical Assessment of Fluctuation (CAF)

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. Higher scores indicate more severe fluctuations while lower scores indicate less severe fluctuations.

Time frame:
Change from Baseline in Clinical Assessment of Fluctuation at 6 months
Reported as:
Mean · score on a scale
Measure the Effects of Nilotinib on Behavior Using the Clinical Assessment of Fluctuation (CAF)
score on a scalePlacebo200 mg Nilotinib
CAF Total-0.05 ± 2.55-0.89 ± 2.45
CAF Total (Baseline)4.73 ± 3.444.38 ± 2.92
CAF Total (6mths)4.74 ± 3.353.39 ± 3.26
Other pre-specifiedMeasure the Effects of Nilotinib on Behavior Using the Irritability-Apathy Scale (IAS)

The IAS measures apathy and irritability in patients with dementia. The IAS is a 14-item self-administered questionnaire collecting information about different aspects of irritability and apathy utilizing a 0-3 scale for each item to indicate severity (0 (absent) to 3 (maximum intensity) per question). Total Range is 0-42; a higher total score indicates more severe symptoms, which are often associated with greater morbidity and worse functional outcomes while a lower score indicates lower severity.

Time frame:
Change from Baseline in Irritability-Apathy Scale at 6 months
Reported as:
Mean · points on a scale
Measure the Effects of Nilotinib on Behavior Using the Irritability-Apathy Scale (IAS)
points on a scalePlacebo200 mg Nilotinib
IAS0.84 ± 3.290.39 ± 3.26
IAS (Baseline)18.59 ± 4.3218.19 ± 3.91
IAS (6mths)19.58 ± 3.5218.56 ± 3.5
Other pre-specifiedMeasure the Effects of Nilotinib on Behavior Using the Problem Behaviors Assessment Short Form (PBA-s)

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. Minimum score is 0 (symptom is absent); maximum score is 176 (11 items × maximum severity 4 × maximum frequency 4). Higher scores indicate increased frequency or severity of behavioral issues while lower scores indicate decreased severity and frequency.

Time frame:
Change from Baseline in Problem Behaviors Assessment short form at 6 months
Reported as:
Mean · points on a scale
Measure the Effects of Nilotinib on Behavior Using the Problem Behaviors Assessment Short Form (PBA-s)
points on a scalePlacebo200 mg Nilotinib
PBA F*S3.95 ± 16.620.17 ± 7.30
PBA F*S (Baseline)17.32 ± 18.4410.29 ± 8.7
PBA F*S (6mths)23.47 ± 24.2810.5 ± 10.54
Other pre-specifiedMeasure the Effects of Nilotinib on Motor Function by Using the Unified Parkinson's Disease Rating Scale (UPDRS)-I-III.

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. The minimum possible score on the UPDRS is 0, which indicates no disability or no symptoms of Parkinson's disease. The scale, used to assess severity, typically ranges from 0 to 199 (total) (199 being the maximum) or 0 to 108 (motor section, Part III) (108 being maximum). Higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-III indicate increased severity of disease, greater disability, and more significant impairment, while lower scores signify better function.

Time frame:
Change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS)-I-III at 6 months
Reported as:
Mean · points on a scale
Measure the Effects of Nilotinib on Motor Function by Using the Unified Parkinson's Disease Rating Scale (UPDRS)-I-III.
points on a scalePlacebo200 mg Nilotinib
(UPDRS)-I-III2.32 ± 9.212.72 ± 6.29
(UPDRS)-I-III (Baseline)38.32 ± 12.1838.21 ± 9.39
(UPDRS)-I-III (6mths)40.63 ± 14.3741.17 ± 11.48
Other pre-specifiedMeasure the Effects of Nilotinib on Motor Function by Using the Timed-Up-And-Go (TUG).

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. A score of less than 10 seconds is normal, 14-20 seconds indicates a high fall risk or frailty, and over 30 seconds suggests significant mobility impairment.

Time frame:
Change from Baseline in Timed-Up-And-Go at 6 months
Reported as:
Mean · seconds
Measure the Effects of Nilotinib on Motor Function by Using the Timed-Up-And-Go (TUG).
secondsPlacebo200 mg Nilotinib
TUG1.16 ± 4.650.06 ± 1.95
TUG (Baseline)12.31 ± 3.2512.63 ± 2.89
TUG (6mths)13.47 ± 6.0812.33 ± 2.91

Adverse events

Collected over Adverse events were collected for 6 months for each participant.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/22 (0%)2/22 (9.1%)15/22 (68.2%)
200 mg Nilotinib0/21 (0%)2/21 (9.5%)11/21 (52.4%)
Most frequent serious events
Most frequent serious events
EventPlacebo200 mg Nilotinib
DyskinesiaNervous system disorders0/221/21
FallInjury, poisoning and procedural complications0/221/21
Atrial fibrillationCardiac disorders1/220/21
AppendectomyGastrointestinal disorders1/220/21
Most frequent other events
Most frequent other events
EventPlacebo200 mg Nilotinib
Joint and Muscle painMusculoskeletal and connective tissue disorders7/224/21
FallsInjury, poisoning and procedural complications6/224/21
COVID-19Respiratory, thoracic and mediastinal disorders4/223/21
RashSkin and subcutaneous tissue disorders2/223/21
LesionsSkin and subcutaneous tissue disorders1/223/21
HallucinationsNervous system disorders3/220/21
EcchymosisCardiac disorders2/220/21
Urinary Tact InfectionRenal and urinary disorders2/221/21
Tissue massNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/220/21

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Placebo200 mg NilotinibTotal
<=18 years000
Between 18 and 65 years000
>=65 years222143
Age, Continuous
Age, Continuous(years)Placebo200 mg NilotinibTotal
Mean73 ± 773 ± 1073 ± 8
Sex: Female, Male
Sex: Female, Male(Participants)Placebo200 mg NilotinibTotal
Female7714
Male151429
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo200 mg NilotinibTotal
American Indian or Alaska Native000
Asian112
Native Hawaiian or Other Pacific Islander000
Black or African American101
White181634
More than one race000
Unknown or Not Reported246
08

Study locations

1 site
  • MedStar Georgetown University Hospital
    Washington D.C., District of Columbia 20007, United States
09

References and documents

Publications

  • Hebron ML, Lonskaya I, Moussa CE. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of alpha-synuclein in Parkinson's disease models. Hum Mol Genet. 2013 Aug 15;22(16):3315-28. doi: 10.1093/hmg/ddt192. Epub 2013 May 10. PubMed 23666528 ↗

Study documents

  • Protocol and statistical analysis plan · Jun 23, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 12, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04002674
Lead sponsor
Georgetown University
Collaborators
National Institutes of Health (NIH)
Responsible party
Fernando Pagan MD (Associate Professor, Department of Neurology Co-Director, Movement Disorders Program Director, NPF Center of Excellence Associate Professor, SOM Clinical Track, Georgetown University) — Principal investigator
First posted
Jun 28, 2019
Start date
Jul 1, 2019
Primary completion
Apr 30, 2025
Completion
Apr 30, 2025
Results posted
Apr 3, 2026
Last update
Jun 12, 2026

Study contacts

Fernando L Pagan, MD
principal investigator · Georgetown University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.

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