NCT04002674

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

Completed Phase 2 Results posted Last updated 3 April 2026

What this trial tests

Phase 2 trial testing Placebo oral capsule in Dementia With Lewy Bodies in 43 participants. Completed in 30 April 2025.

Timeline

1 July 2019

Primary endpoint
30 April 2025

30 April 2025

Quick facts

Lead sponsor	Georgetown University
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	43
Start date	1 July 2019
Primary completion	30 April 2025
Estimated completion	30 April 2025
Sites	1 location across United States

Drugs / interventions tested

• Placebo oral capsule
• Nilotinib Oral Capsule

Conditions studied

• Dementia With Lewy Bodies — all drugs for Dementia With Lewy Bodies →

Sponsor

Georgetown University

Who can join

Adults 25 to 90, any sex, with Dementia With Lewy Bodies. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety and Tolerability: Occurrence of Adverse Events (AEs) Primary · 6 Months

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

Severe Adverse Events

Group	Value	95% CI
Placebo	2
200 mg Nilotinib	2

Adverse Events

Group	Value	95% CI
Placebo	74
200 mg Nilotinib	37

Falls

Group	Value	95% CI
Placebo	21
200 mg Nilotinib	6

DLB Related CSF Biomarkers Secondary · 6 Months

Pharmacodynamics: Determine the effects of Nilotinib on primary biomarkers

Amyloid beta-42

Group	Value	95% CI
Placebo	234.1	± 72.15
200 mg Nilotinib	358.6	± 183.9

phospho-Tau (181)

Group	Value	95% CI
Placebo	74.89	± 44.85
200 mg Nilotinib	48.13	± 22.64

Total alpha synuclein

Group	Value	95% CI
Placebo	1685	± 988.5
200 mg Nilotinib	1269	± 498.6

Matrix metalloprotease-10

Group	Value	95% CI
Placebo	29.41	± 17.26
200 mg Nilotinib	19.21	± 8.848

DLB Related CSF Biomarkers Secondary · Changes from Baseline to 6 months

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

Change from Baseline

Group	Value	95% CI
Placebo	-40.90	± 68.3
200 mg Nilotinib	57.64	± 109.2

Baseline

Group	Value	95% CI
Placebo	224.6	± 149.2
200 mg Nilotinib	277.1	± 264.9

End of Treatment (EOT)

Group	Value	95% CI
Placebo	183.7	± 105
200 mg Nilotinib	334.8	± 285.3

DLB Related CSF Biomarkers Secondary · 6 months

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

Group	Value	95% CI
Placebo	0.3081	± 0.2248
200 mg Nilotinib	0.1764	± 0.1254

Measure the Effects of Nilotinib on Cognition Using the Montreal Cognitive Assessment (MoCA) Secondary · Change from Baseline in the Montreal Cognitive Assessment at 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; a score of 26 or higher is generally considered normal, while lower scores indicate impairment.

MOCA

Group	Value	95% CI
Placebo	-1.37	± 3.02
200 mg Nilotinib	0.11	± 1.71

MOCA (Baseline)

Group	Value	95% CI
Placebo	23.68	± 5.26
200 mg Nilotinib	25.26	± 3.33

MOCA (6mths)

Group	Value	95% CI
Placebo	22.32	± 5.68
200 mg Nilotinib	25.44	± 3.94

Measure the Effects of Nilotinib on Cognition Using the Trail Making Test (TMT) Secondary · Change from Baseline in the Trail Making Test at 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. Lower times indicate better executive function, while higher scores suggest impairment.

TMT

Group	Value	95% CI
Placebo	12.60	± 33.36
200 mg Nilotinib	-2.44	± 72.87

TMT (Baseline)

Group	Value	95% CI
Placebo	213.63	± 88.96
200 mg Nilotinib	196.68	± 79.10

TMT (6 mths)

Group	Value	95% CI
Placebo	227.67	± 90.85
200 mg Nilotinib	200.94	± 74.38

Measure the Effects of NIlotinib on Cognition Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog14). Secondary · Change from Baseline in the Alzheimer's Disease Assessment Scale - cognitive at 6 months

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

ADAS-Cog

Group	Value	95% CI
Placebo	2.46	± 6.12
200 mg Nilotinib	-0.70	± 5.36

ADAS-Cog (Baseline)

Group	Value	95% CI
Placebo	25.88	± 10.76
200 mg Nilotinib	24.20	± 10.98

ADAS-Cog (6mths)

Group	Value	95% CI
Placebo	28.33	± 12.60
200 mg Nilotinib	23.50	± 13.08

Measure the Effects of Nilotinib on Behavior Using the Alzheimer's Disease Cooperative Study-Activity of Daily Living Scale (ADCS-ADL) Secondary · Change from Baseline in the Alzheimer's Disease Cooperative Study-Activity of Daily Living Scale at 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.

ADCS-ADL

Group	Value	95% CI
Placebo	-4.47	± 8
200 mg Nilotinib	-1.22	± 3.61

ADCS-ADL (Baseline)

Group	Value	95% CI
Placebo	65.72	± 13.47
200 mg Nilotinib	72	± 6.7

ADCS-ADL (6mths)

Group	Value	95% CI
Placebo	61.25	± 15.7
200 mg Nilotinib	70.78	± 7.64

Measure the Effects of Nilotinib on Behavior Using the Neuropsychiatric Inventory (NPI) Secondary · Change from Baseline in Neuropsychiatric Inventory at 6 months

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

NPI

Group	Value	95% CI
Placebo	3.37	± 12.13
200 mg Nilotinib	0.17	± 7.33

NPI (Baseline)

Group	Value	95% CI
Placebo	13.86	± 15.38
200 mg Nilotinib	11.10	± 8.65

NPI (6mths)

Group	Value	95% CI
Placebo	18.32	± 17.85
200 mg Nilotinib	10.89	± 9.16

Measure the Effects of Nilotinib on Behavior Using the Clinical Assessment of Fluctuation (CAF) Secondary · Change from Baseline in Clinical Assessment of Fluctuation at 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. Higher scores indicate more severe fluctuations while lower scores indicate less severe fluctuations.

CAF Total

Group	Value	95% CI
Placebo	-0.05	± 2.55
200 mg Nilotinib	-0.89	± 2.45

CAF Total (Baseline)

Group	Value	95% CI
Placebo	4.73	± 3.44
200 mg Nilotinib	4.38	± 2.92

CAF Total (6mths)

Group	Value	95% CI
Placebo	4.74	± 3.35
200 mg Nilotinib	3.39	± 3.26

Measure the Effects of Nilotinib on Behavior Using the Irritability-Apathy Scale (IAS) Secondary · Change from Baseline in Irritability-Apathy Scale at 6 months

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.

IAS

Group	Value	95% CI
Placebo	0.84	± 3.29
200 mg Nilotinib	0.39	± 3.26

IAS (Baseline)

Group	Value	95% CI
Placebo	18.59	± 4.32
200 mg Nilotinib	18.19	± 3.91

IAS (6mths)

Group	Value	95% CI
Placebo	19.58	± 3.52
200 mg Nilotinib	18.56	± 3.5

Measure the Effects of Nilotinib on Behavior Using the Problem Behaviors Assessment Short Form (PBA-s) Secondary · Change from Baseline in Problem Behaviors Assessment short form at 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

PBA F*S

Group	Value	95% CI
Placebo	3.95	± 16.62
200 mg Nilotinib	0.17	± 7.30

PBA F*S (Baseline)

Group	Value	95% CI
Placebo	17.32	± 18.44
200 mg Nilotinib	10.29	± 8.7

PBA F*S (6mths)

Group	Value	95% CI
Placebo	23.47	± 24.28
200 mg Nilotinib	10.5	± 10.54

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected for 6 months for each participant.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 2/22 (9%)

Deaths: 0/22

200 mg Nilotinib

Serious: 2/21 (10%)

Deaths: 0/21

Serious adverse events (4 terms)

Reaction	System	Placebo	200 mg Nilotinib
Atrial fibrillation	Cardiac disorders	—	—
Appendectomy	Gastrointestinal disorders	—	—
Dyskinesia	Nervous system disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Placebo	200 mg Nilotinib
Joint and Muscle pain	Musculoskeletal and connective tissue disorders	—	—
Falls	Injury, poisoning and procedural complications	—	—
COVID-19	Respiratory, thoracic and mediastinal disorders	—	—
Hallucinations	Nervous system disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Lesions	Skin and subcutaneous tissue disorders	—	—
Ecchymosis	Cardiac disorders	—	—
Urinary Tact Infection	Renal and urinary disorders	—	—
Tissue mass	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—

Most-reported serious reactions: Atrial fibrillation, Appendectomy, Dyskinesia, Fall.

Data from ClinicalTrials.gov NCT04002674 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.