ATX-001

CompletedPhase 2Results posted

Effects of Atomoxetine in Mild Cognitive Impairment

A 6 Month, Phase II Randomized, Double-Blind, Placebo Controlled, Flexible Dosing, Crossover Trial of Atomoxetine in Subjects With Mild Cognitive Impairment.

Lead sponsor

Emory University

Asset

Atomoxetine

Listed sites

Recruiting sites

Enrollment

actual

Study population

MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•Tau biomarker required (CSF)•Study partner/caregiver required

Primary endpoints

•Interleukin 1 (IL 1-alpha) in Cerebrospinal Fluid (CSF)•Mean Level of Thymus-Expressed Chemokine (TECK) in Cerebrospinal Fluid (CSF)•Number of All Adverse Events Among the Participants With Mild Cognitive

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Nih5U01AG010483

Secondary IDATX-001Other

Org study IDIRB00054397

NCT IDNCT01522404

Timeline

Milestones

Study first posted2012-01-31estimated

Study start2012-03actual (month precision)

Primary completion2017-10-31actual

Study completion2018-06-30actual

Results first posted2018-12-05actual

Last update posted2019-07-23actual

Assets

Drug assets

Atomoxetine

Study populations

Who this study enrolls

MCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Eligibility criteria

Inclusion

•Subjects must have a subjective memory concern as reported by subject, study partner or clinician.

•Meets Alzheimer's Disease Neuroimaging Initiative (ADNI) criteria for diagnosis of MCI. Subjects with amnestic (single or multi-domain) will be eligible, as both subtypes of MCI are at high risk for progression to AD.

•Abnormal memory function documented by assessment using the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25):

-<11 for 16 or more years of education

-<9 for 8-15 years of education

-<6 for <7 years of education

•Mini-Mental State Exam score between 24 and 30 (inclusive). Exceptions may be made for subjects with less than 8 years of education at the discretion of the PI.

•Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.

•General cognition and functional performance sufficiently preserved such that a diagnosis of AD cannot be made by the physician at the time of the screening visit.

•Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen.

•Stability of Permitted Medications for 4 weeks. In particular, subjects may washout from excluded medication for at least 4 weeks prior to screening.

•Geriatric Depression Scale (GDS) ≤ than 6.

•Male or female outpatients aged 50-90 (inclusive).

•Study partner has regular contact with the subject adequate to provide a reliable assessment of the subject's level of function, and can be available for all clinic visits, either in person or by telephone, for the duration of the study.

•Visual and auditory acuity adequate for neuropsychological testing.

•Good general health with no diseases expected to interfere with the study.

•For women of child-bearing potential (i.e., one who is biologically capable of becoming pregnant), must be willing to use a medically acceptable form or birth control or practice abstinence for the duration of her participation in the trial. Acceptable methods of birth control include: oral or patch contraception, or medroxyprogesterone (Depo-Provera®) or other intramuscular contraceptive injection, or implantation of levonorgestrel (Norplant®) system, an Intrauterine Device (IUD), a reliably-employed barrier method (e.g. diaphragm, cervical cap or condom), or a male partner who is surgically sterilized.

•Modified Rosen Hachinski ≤ 4.

•Completed six grades of education or has a good work history (sufficient to exclude mental retardation).

•Able to communicate in English with study personnel.

•Able to understand the nature of the study and must provide written informed consent prior to conduct of any study procedures.

•Willing to undergo repeated MRIs (3Tesla) and at least three Positron-Emission Tomography (PET) scans. No medical contraindications to MRI.

•Agrees to blood collection for Apolipoprotein (APOE) epsilon, CYP2D6 and biomarker testing.

•Agrees to lumbar puncture over the course of the study for the collection of CSF. CSF levels of Ab42, total Tau, and Tau phosphorylated at threonine 181 consistent with underlying AD pathology according to established threshold values at Emory and the ADNI Biomarker Core

Exclusion

•Any significant neurologic disease other than MCI and suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, poorly controlled seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.

•Screening/baseline MRI scan with evidence of infection, large vessel infarction or other focal structural lesions that could account for the memory deficits. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.

•Contraindication to MRI due to presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, or excessive weight.

•Presence of clinically significant suicide risk, based on the Investigator's judgment informed by a structured clinician interview. Any suicide attempt within the past 1 year of the screening visit is exclusionary.

•Major depression, bipolar disorder as described in DSM-IV within the past 1 year, or history of schizophrenia (DSM-IV). Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.

•History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria).

•Allergic to any component of atomoxetine (Strattera).

•Any uncontrolled medical condition that is expected to preclude completion of the study, or any medical condition which would represent a contraindication to atomoxetine pharmacotherapy (e.g. hepatic insufficiency, untreated hypertension, untreated cardiovascular or cerebrovascular disease).

•Known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems.

•History of narrow angle glaucoma.

•History of pheochromocytoma.

•Clinically significant abnormal findings on screening laboratory tests or physical exam. Abnormalities in Vitamin B12 level, Thyroid Function Tests (TFTs) or Liver Function Tests (LFTs) that might interfere with the study. A low Vitamin B12 level is exclusionary, unless follow-up labs (homocysteine and methylmalonic acid indicate that it is not physiologically significant.

•Slow metabolizer of atomoxetine (i.e., CYP2D6 polymorphism).

•Women who are pregnant or lactating, or who plan to become pregnant during the study.

•Current use of warfarin (exclusionary for lumbar puncture).

•Inability to obtain initial CSF sample.

•Use within 60 days of a monoamine oxidase inhibitor or a potent CYP2D6 inhibitor.

•Current use of anti-psychotic medication.

•Current use of the following anti-depressant medications that act on NET: duloxetine, venlafaxine, desvenlafaxine, imipramine, or amitryptiline.

•Current participation in another clinical trial. Participation in clinical studies involving neuropsychological measures being collected more than one time per year.

•CSF profile is not consistent with underlying Alzheimer's Disease pathology.

•Reasonable likelihood for non-compliance with the protocol or any other reason, in the opinion of the investigator, prohibits enrollment of subject into the study.

•Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director.

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Neuroimaging

Fluid / digital biomarkers

Safety / tolerability / PK

Neuroimaging

4 endpoints

Secondary/protocol endpoint

Rate of Cerebral Blood Flow in Subjects With Mild Cognitive Impairment MCI Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine

Time frame:Baseline, Week 29, Week 58

change from baseline, improvement

Secondary/protocol endpoint

Change in FluoroDeoxyGlucose (FDG) Uptake in Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine

Time frame:Baseline, Week 29 and Week 58

change from baseline, improvement

Secondary/registry result

Rate of Cerebral Blood Flow in Subjects With Mild Cognitive Impairment MCI Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine

Time frame:Baseline, Week 29, Week 58

change from baseline, improvement

Posted result

Group	Value (mean), mL/100 g/min	Standard deviation
Atomoxetine / Inactive CompoundBaselinen=17 Participants	42.4	8.6
Week 29n=17 Participants	39.3	5.6
Week 58n=17 Participants	40.2	7.1
Inactive Compound / AtomoxetineBaselinen=19 Participants	42.6	7.5
Week 29n=19 Participants	38.8	6.2
Week 58n=19 Participants	39.6	8.0

Secondary/registry result

Time frame:Baseline, Week 29 and Week 58

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Standard deviation
Atomoxetine / Inactive CompoundBaselinen=17 Participants	0.69	0.07
Week 29n=17 Participants	0.72	0.08
Week 58n=17 Participants	0.74	0.09
Inactive Compound / AtomoxetineBaselinen=19 Participants	0.68	0.08
Week 29n=19 Participants	0.67	0.10
Week 58n=19 Participants	0.73	0.08

Fluid / digital biomarkers

4 endpoints

Primary/protocol endpoint

Change in Interleukin 1 (IL 1-alpha) in Cerebrospinal Fluid (CSF) in Subjects With Mild Cognitive Impairment (MCI) Treated With Atomoxetine/Inactive Compound Compared to Subjects Treated With Inactive Compound / Atomoxetine

Time frame:Baseline, Week 29 and Week 58

change from baseline, improvement

Primary/protocol endpoint

Change in Mean Level of Thymus-Expressed Chemokine (TECK) in Cerebrospinal Fluid (CSF) in Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine / Inactive Compound Compared to Participants Treated With Inactive Compound / Atomoxetine

Time frame:Baseline, Week 29 and Week 58

change from baseline, improvement

Primary/registry result

Time frame:Baseline, Week 29 and Week 58

change from baseline, improvement

Primary/registry result

Time frame:Baseline, Week 29 and Week 58

change from baseline, improvement

Posted result

Group	Value (mean), pg/mL	Standard deviation
AtomoxetineBaselinen=18 Participants	1	0.4
Week 29n=18 Participants	1	0.4
Week 58n=18 Participants	1.1	0.7
Inactive Compound / PlaceboBaselinen=18 Participants	0.8	0.2
Week 29n=18 Participants	0.9	0.2
Week 58n=18 Participants	0.9	0.3

Safety / tolerability / PK

4 endpoints

Primary/protocol endpoint

Number of All Adverse Events Among the Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine Compared to the Participants Treated With Placebo/Inactive Compound

Time frame:Up to Week 58

event count, event

Primary/protocol endpoint

Number of Participants That Drop Out of the Study Among the Participants Treated With Atomoxetine When Compared to the Participants Treated With Inactive Compound (Placebo)

Time frame:Up to Week 58

event count, event

Primary/registry result

Number of All Adverse Events Among the Participants With Mild Cognitive Impairment (MCI) Treated With Atomoxetine Compared to the Participants Treated With Placebo/Inactive Compound

Time frame:Up to Week 58

event count, event

Posted result

Group	Value (number), Adverse events	Reported bounds
Atomoxetinen=39 Participants	142	-
Inactive Compound (Placebo)n=37 Participants	91	-

Primary/registry result

Number of Participants That Drop Out of the Study Among the Participants Treated With Atomoxetine When Compared to the Participants Treated With Inactive Compound (Placebo)

Time frame:Up to Week 58

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Atomoxetinen=39 Participants	2	-
Inactive Compound/Placebon=37 Participants	1	-

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.