Alzheimer's DiseasePhase 2ADNCT02947893
Impact of Nilotinib on Safety, Biomarkers and Clinical Outcomes in Mild to Moderate Alzheimer's Disease
A Phase 2 study testing Nilotinib Capsule(s) Once a Day by Mouth in people with Alzheimer's Disease, run by Georgetown University at 1 site in United States.
Trial summary
The investigators hypothesize that Nilotinib will be safe in individuals with mild to moderate AD. Specifically, investigators hypothesize that low daily oral doses of Nilotinib will lead to CSF penetration, CNS Abl inhibition, and stabilization of CSF total Tau and p-Tau231/181 and Abeta42/40 levels. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Nilotinib Capsule(s) Once a Day by Mouth
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to Mar 2021
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 50
- Fluent in English
- Biomarker confirmed AD with CSF level of Abeta42 <600ng/mL
- Able to ingest oral medications
- Diagnosis of mild to moderate AD according to dementia criteria outlined by McKhann et al.
- Neuroimaging (MRI or CT) consistent with the diagnosis of AD within the past year
Show all 19Show fewer
- MMSE between 17 and 24 (inclusive) at screening
- Modified Hachinski score ≤ 4
- QTc interval 350-460ms, inclusive
- Caregiver/study partner to accompany participant to all visits and have direct contact with the participant > 2 days/week
- Written informed consent
- Capability and willingness to comply with all study criteria
- Supervision available for study medication
- Stable medical conditions for 3 months prior to screening visit
- Stable medications for 4 weeks prior to screening visit
- Able to complete baseline assessments
- Minimum of 6 years of education, or work history sufficient to exclude mental retardation
- Stable use of cholinesterase inhibitors and memantine (U.S. FDA-approved medications for patients with probable AD), vitamin E (up to 400 IU daily), estrogens, aspirin (81-300 mg daily), and cholesterol-lowering agents for 3 months prior to screening is allowed.
- Clinical laboratory values within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
Who cannot join
- Non-AD dementia, probable AD with Down syndrome, APP, PS-1, or PS-2 mutations (known familial AD), LBD and Fronto-temporal dementia (FTD)
- History of clinically significant stroke
- 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
- Sensory impairment that would preclude participation/cooperation with the protocol
- Patients with hypokalemia, hypomagnesaemia, or long QTc syndrome.
- Concomitant drugs known to prolong the QTc interval (>461ms) and history of cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia
Show all 16Show fewer
- Prescribed strong CYP3A4 inhibitors or a medical history of liver or pancreatic disease
- 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
- Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history of treated basal or squamous skin cancer, or stable prostate cancer are not exclusionary)
- Pregnancy or possible pregnancy
- 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
- Contraindication to MRI
- Evidence of more than 4 micro hemorrhages and/or hemosiderosis by a recent (12 months) and/or the screening MRI.
- A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
- Enrolled in another active trial investigating an experimental drug or therapy for AD
- HIV positive
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgetown University Medical Center
Washington D.C., District of Columbia, 20057
About this study
Official title: A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Low Doses of Nilotinib (Tasigna®) on Safety, Biomarkers and Clinical Outcomes in Subjects With Mild to Moderate Alzheimer's Disease
The investigators hypothesize that Nilotinib will be safe in individuals with mild to moderate AD. Specifically, investigators hypothesize that low daily oral doses of Nilotinib will lead to CSF penetration, CNS Abl inhibition, and stabilization of CSF total Tau and p-Tau231/181 and Abeta42/40 levels. The investigators hypothesize that Nilotinib will decrease brain load of amyloid using amyloid positron emission tomography (PET). The investigators also predict that Nilotinib will reduce CSF markers of cell death, including neuron specific enolase (NSE) and S100B.
Read the detailed description
The investigators propose a novel treatment strategy that involves Abl inhibition to alter Abeta40/42, total Tau and p-Tau231/181 in subjects with mild to moderate dementia due to AD. The goal of this study is to evaluate the impact of low dose Nilotinib on safety, biomarkers and clinical symptoms in patients with mild to moderate AD. Forty two (42) participants with mild to moderate and their study partners will be recruited and randomly assigned 1:1 to group 1 (placebo) for one year or group 2 treated with 150mg Nilotinib for 6 months followed by dose escalation to 300mg once for 12 months.
Primary outcomes, we will evaluate the effects of Nilotinib on: Safety and tolerability: Safety will be measured using the occurrence of adverse events (AEs) and serious adverse events (SAEs) deemed to be possibly, probably, or definitely related to the study drug. Tolerability for a given participant will be defined as the ability of participants to remain on treatment. Overall tolerability of the drug will be defined as less than 25% discontinuations due to drug-related AEs and SAEs. Secondary outcomes, we will determine the effects of Nilotinib treatment on measurement of Nilotinib in the CSF and Abl inhibition to demonstrate CNS target engagement and changes of AD related CSF and plasma levels of Abeta42/40, total Tau and p-Tau231/181. Exploratory outcomes will include assessment of: Cognitive function via MMSE, AD Assessment Scale-Cognitive subscale (ADAS-cog), AD Cooperative Study-Activity of Daily Living (ADCS-ADL), Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB), and Neuropsychiatric Inventory (NPI).
- Conditions
- Alzheimer's Disease
- Being tested
- Placebo Capsule(s) Once a Day by Mouth, Nilotinib Capsule(s) Once a Day by Mouth
- Keywords
- Nilotinib in Alzheimer's disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Capsule(s) Once a Day by MouthDrug
1 capsule of Placebo once a day for 6 months followed by 2 capsules of Placebo for another 6 months
Nilotinib Capsule(s) Once a Day by MouthDrug
1 capsule of Nilotinib 150 mg once a day for 6 months followed by 2 capsules of Nilotinib (150 mg each capsule = 300 mb total) for the subsequent 6 months
| Study group | Role | What they receive |
|---|---|---|
| Group 1 (placebo) | Placebo comparator | Out of 42 total participants with mild to moderate AD (MMSE=17-24 inclusive) and their study partners that will be recruited and 1:1 randomized, 21 (twenty-one) will be assigned to group 1 and given 1 capsule of a placebo drug by mouth every day for the first 6 months followed by 2 capsules once daily for the subsequent 6 months, every time taken without a meal, for the total duration of the study for 12 months. Receives: Drug: Placebo Capsule(s) Once a Day by Mouth |
| Group 2 (treated) | Active comparator | Out of 42 total participants with mild to moderate AD (MMSE=17-24 inclusive) and their study partners that will be recruited and 1:1 randomized, 21 (twenty-one) will be assigned to group 2 treated with 1 capsule (150mg Nilotinib) once a day by mouth for the first 6 months followed by dose escalation to 2 capsules (300mg Nilotinib) once daily by mouth for the subsequent 6 months, every time taken without a meal, for the total study duration of 12 months. Receives: Drug: Nilotinib Capsule(s) Once a Day by Mouth |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Will be Measured by Number of Participants Experiencing the Occurrence of Adverse Events and/or Abnormal Laboratory Values
Safety will be measured by assessing number of participants with abnormal laboratory values, as well as adverse events (AEs) and serious adverse events (SAEs) deemed to be possibly, probably, or definitely related to the study drug.
Measured: 12 months
Secondary outcomes (3)
Pharmacokinetics of Nilotinib in Individuals With Alzheimer's Disease
To determine the Cmax (ng/ml), we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Measured: 12 months
Pharmacokinetics of Nilotinib in Individuals With Alzheimer's Disease
To determine the Tmax, we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Measured: 12 months
Pharmacokinetics of Nilotinib in Individuals With Alzheimer's Disease
To determine the AUC (ng/ml*h) , we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2016 (estimated)
- Study startJan 2017
- Primary completionDec 2020
- Study completionMar 2021
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 (2)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 Georgetown UniversityThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, R. Scott Turner, Georgetown University
- Investigators
- Raymond S Turner, MD, PhD, Principal investigator, Georgetown UniversityCharbel E Moussa, MBBS, PhD, Study director, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02947893
- Sponsor's protocol ID
- 2016-0315
- Acronym
- AD
- Status last verified
- Jun 2026
- First submitted
- 21 Oct 2016
- Last updated
- 23 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Pagan F, Hebron M, Valadez EH, Torres-Yaghi Y, Huang X, Mills RR, Wilmarth BM, Howard H, Dunn C, Carlson A, Lawler A, Rogers SL, Falconer RA, Ahn J, Li Z, Moussa C. Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies. J Parkinsons Dis. 2016 Jul 11;6(3):503-17. doi: 10.3233/JPD-160867.
PubMed 27434297Pagan FL, Hebron ML, Wilmarth B, Torres-Yaghi Y, Lawler A, Mundel EE, Yusuf N, Starr NJ, Anjum M, Arellano J, Howard HH, Shi W, Mulki S, Kurd-Misto T, Matar S, Liu X, Ahn J, Moussa C. Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2020 Mar 1;77(3):309-317. doi: 10.1001/jamaneurol.2019.4200.
PubMed 31841599
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Low Doses of Nilotinib (Tasigna®) on Safety, Biomarkers and Clinical Outcomes in Subjects With Mild to Moderate Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT02947893
- Acronym / sponsor ID
- AD / 2016-0315
- Conditions
- Alzheimer's Disease
- Keywords
- Nilotinib in Alzheimer's disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Dec 2020 (actual)
- Study completion
- Mar 2021 (actual)
- First posted
- 28 Oct 2016 (estimated)
- Results
- Posted 23 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that Nilotinib will be safe in individuals with mild to moderate AD. Specifically, investigators hypothesize that low daily oral doses of Nilotinib will lead to CSF penetration, CNS Abl inhibition, and stabilization of CSF total Tau and p-Tau231/181 and Abeta42/40 levels. The investigators hypothesize that Nilotinib will decrease brain load of amyloid using amyloid positron emission tomography (PET). The investigators also predict that Nilotinib will reduce CSF markers of cell death, including neuron specific enolase (NSE) and S100B.
Detailed description
The investigators propose a novel treatment strategy that involves Abl inhibition to alter Abeta40/42, total Tau and p-Tau231/181 in subjects with mild to moderate dementia due to AD. The goal of this study is to evaluate the impact of low dose Nilotinib on safety, biomarkers and clinical symptoms in patients with mild to moderate AD. Forty two (42) participants with mild to moderate and their study partners will be recruited and randomly assigned 1:1 to group 1 (placebo) for one year or group 2 treated with 150mg Nilotinib for 6 months followed by dose escalation to 300mg once for 12 months.
Primary outcomes, we will evaluate the effects of Nilotinib on: Safety and tolerability: Safety will be measured using the occurrence of adverse events (AEs) and serious adverse events (SAEs) deemed to be possibly, probably, or definitely related to the study drug. Tolerability for a given participant will be defined as the ability of participants to remain on treatment. Overall tolerability of the drug will be defined as less than 25% discontinuations due to drug-related AEs and SAEs. Secondary outcomes, we will determine the effects of Nilotinib treatment on measurement of Nilotinib in the CSF and Abl inhibition to demonstrate CNS target engagement and changes of AD related CSF and plasma levels of Abeta42/40, total Tau and p-Tau231/181. Exploratory outcomes will include assessment of: Cognitive function via MMSE, AD Assessment Scale-Cognitive subscale (ADAS-cog), AD Cooperative Study-Activity of Daily Living (ADCS-ADL), Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB), and Neuropsychiatric Inventory (NPI).
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 |
|---|---|---|
| Group 1 (placebo) | Placebo comparator | Drug: Placebo Capsule(s) Once a Day by MouthOut of 42 total participants with mild to moderate AD (MMSE=17-24 inclusive) and their study partners that will be recruited and 1:1 randomized, 21 (twenty-one) will be assigned to group 1 and given 1 capsule of a placebo drug by mouth every day for the first 6 months followed by 2 capsules once daily for the subsequent 6 months, every time taken without a meal, for the total duration of the study for 12 months. |
| Group 2 (treated) | Active comparator | Drug: Nilotinib Capsule(s) Once a Day by MouthOut of 42 total participants with mild to moderate AD (MMSE=17-24 inclusive) and their study partners that will be recruited and 1:1 randomized, 21 (twenty-one) will be assigned to group 2 treated with 1 capsule (150mg Nilotinib) once a day by mouth for the first 6 months followed by dose escalation to 2 capsules (300mg Nilotinib) once daily by mouth for the subsequent 6 months, every time taken without a meal, for the total study duration of 12 months. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age ≥ 50
- Fluent in English
- Biomarker confirmed AD with CSF level of Abeta42 <600ng/mL
- Able to ingest oral medications
- Diagnosis of mild to moderate AD according to dementia criteria outlined by McKhann et al.
Key exclusion criteria (16 listed)
- Non-AD dementia, probable AD with Down syndrome, APP, PS-1, or PS-2 mutations (known familial AD), LBD and Fronto-temporal dementia (FTD)
- History of clinically significant stroke
- 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
- Sensory impairment that would preclude participation/cooperation with the protocol
- Patients with hypokalemia, hypomagnesaemia, or long QTc syndrome.
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 |
|---|---|---|
| Placebo Capsule(s) Once a Day by Mouth1 capsule of Placebo once a day for 6 months followed by 2 capsules of Placebo for another 6 months | Drug | Group 1 (placebo) |
| Nilotinib Capsule(s) Once a Day by Mouth1 capsule of Nilotinib 150 mg once a day for 6 months followed by 2 capsules of Nilotinib (150 mg each capsule = 300 mb total) for the subsequent 6 months | Drug | Group 2 (treated) |
Primary outcome
Safety Will be Measured by Number of Participants Experiencing the Occurrence of Adverse Events and/or Abnormal Laboratory Values
Time frame: 12 months
Safety will be measured by assessing number of participants with abnormal laboratory values, as well as adverse events (AEs) and serious adverse events (SAEs) deemed to be possibly, probably, or definitely related to the study drug.
3 secondary outcomes
Pharmacokinetics of Nilotinib in Individuals With Alzheimer's Disease
Time frame: 12 months
Pharmacokinetics of Nilotinib in Individuals With Alzheimer's Disease
Time frame: 12 months
Pharmacokinetics of Nilotinib in Individuals With Alzheimer's Disease
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27434297Pagan F, Hebron M, Valadez EH, Torres-Yaghi Y, Huang X, Mills RR, Wilmarth BM, Howard H, Dunn C, Carlson A, Lawler A, Rogers SL, Falconer RA, Ahn J, Li Z, Moussa C. Nilotinib Effects in Parkinson's disease and Dementia with Lewy bodies. J Parkinsons Dis. 2016 Jul 11;6(3):503-17. doi: 10.3233/JPD-160867.
- Background: PubMed 31841599Pagan FL, Hebron ML, Wilmarth B, Torres-Yaghi Y, Lawler A, Mundel EE, Yusuf N, Starr NJ, Anjum M, Arellano J, Howard HH, Shi W, Mulki S, Kurd-Misto T, Matar S, Liu X, Ahn J, Moussa C. Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial. JAMA Neurol. 2020 Mar 1;77(3):309-317. doi: 10.1001/jamaneurol.2019.4200.
- MEMORY DISORDERS PROGRAM Georgetown University Medical Center \& Medstar Georgetown University HospitalLink provided by the sponsor.
- 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.
Raymond S Turner, MD, PhD principal investigator
Georgetown University
Charbel E Moussa, MBBS, PhD study director
Georgetown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib Capsule(s) Once a Day by Mouth in people with Alzheimer's Disease, run by Georgetown University at 1 site 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 19 inclusion and 16 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 23 Jul 2026. 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 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 23 Jul 2026). 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?
Safety Will be Measured by Number of Participants Experiencing the Occurrence of Adverse Events and/or Abnormal Laboratory Values (time frame: 12 months). 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 NCT02947893, which also lists 2 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 23 Jul 2026.