BEAT-AD

CompletedPhase 2Results posted

Bexarotene Amyloid Treatment for Alzheimer's Disease

A Double Blind Placebo Controlled Randomized Study to Evaluate the Efficacy and Safety of Bexarotene in Patients With Mild to Moderate Alzheimer's Disease

Lead sponsor

The Cleveland Clinic

Asset

Bexarotene

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 10-20•Study partner/caregiver required•MRI contraindications excluded•ARIA-E/ARIA-H at screening excluded

Primary endpoints

•Drug-Placebo Difference in Change•Primary Outcome by Genotype (ALL SUBJECTS)•Primary Outcome by Genotype (NON ApoE4 CARRIERS)

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

Org study IDCCF-IRB 12-783

NCT IDNCT01782742

Timeline

Milestones

Study start2013-02 (month precision)

Study first posted2013-02-04estimated

Primary completion2014-08actual (month precision)

Study completion2014-12actual (month precision)

Last update posted2016-02-12estimated

Results first posted2016-02-12estimated

Assets

Drug assets

Bexarotene

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Males or females 50 to 90 of age inclusive.

•Diagnosis of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

•Willing and able to provide informed consent by either the subject or subject's legal representative.

•Willing and able to comply with study visits, treatment plan, laboratory tests, brain imaging and other procedures.

•Subjects must have a positive 18f-AV-45 PET scan as determined by a qualified rater.

•Mini-Mental State Examinations (MMSE) score between 10-20 inclusive.

•Must have a study partner who is able and willing to comply with all required study procedures.

•Females must be postmenopausal.

•Have at least eight years of education and should have previously (in pre-AD condition) been capable of reading, writing, and communicating effectively with others in English.

•If receiving therapy with a cholinesterase inhibitor and/or memantine, the dose of these agents has been stable for at least 4 weeks prior to randomization

•Normal laboratory findings at baseline including CBC, chemistry panel, serum lipids, liver functions, TSH, and vitamin B12.

•Must consent to ApoE genotyping

Exclusion criteria

•Any clinically relevant neurological disorder capable of producing a dementia syndrome including Parkinson's disease, stroke, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and others.

•4 or more micro-hemorrhages (amyloid-related imaging abnormalities - hemorrhage type (ARIA-H) on baseline MRI or any evidence of amyloid-related imaging abnormalities - effusion type (ARIA-E) (Sperling et al, 2011).

•History of malignancy within the past five years with the exception of basal cell or squamous cell cancer, in-situ cervical cancer, or localized prostate cancer.

•History of seizure in the past three years prior to randomization

•Any contraindication of having brain MRI

•Any contraindication of having PET (inability to lie flat and still for the duration of the scan, intolerance to previous PET such as hypersensitivity reaction to PET ligand or imaging agent)

•The subject has any unstable medical illness including hypertension, congestive heart failure, chronic obstructive pulmonary disease, renal failure, liver failure or other organ compromise.

•Other clinically important abnormality on vital signs, physical examination, neurologic examination, laboratory results, or electrocardiogram (ECG) examination (e.g. Atrial fibrillation) that could compromise the study or be detrimental to the subject.

•The subject has received bexarotene previously.

•The subject has an allergy to bexarotene.

•Has had a PET scan in the past 12 months.

•Has had radiotherapy in the past year.

•Have participated in an investigational drug or device study within 30 days prior to Visit 2.

•Have been treated with immunomodulators to treat AD (vaccines, antibodies etc) within 6 months prior to visit 2

•Unable to swallow uncrushed oral medication in capsule form

•Have any condition or reason that, in the opinion of the investigator, which could interfere with the ability of the patients to participate or complete the trials, or places the patient at undue risk or complicates the interpretation of safety or efficacy data.

Endpoints (30)

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

Amyloid biomarkers

Global cognition

Other (unclassified)

Function / daily living

Behavior / neuropsychiatric

Global cognition

6 endpoints

Secondary/protocol endpoint

Change in MMSE Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/registry result

Change in MMSE Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), points	Reported bounds
Bexarotenen=16 Participants	0.750	--0.783 - 2.283
Placebon=4 Participants	1.750	--1.316 - 4.816

Mean Difference (Final Values)-1.00095% CI-4.428 - 2.428p0.57t-test, 2 sided

Secondary/registry result

Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), points	Reported bounds
Bexarotenen=16 Participants	0.375	--2.153 - 2.903
Placebon=4 Participants	-0.250	--5.307 - 4.807

Mean Difference (Final Values)0.62595% CI-5.029 - 6.279p0.83t-test, 2 sided

Secondary/registry result

Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), units on a scale	Reported bounds
Bexarotenen=16 Participants	0.000	-0.000 - 0.000
Placebon=4 Participants	0.000	-0.000 - 0.000

Mean Difference (Final Values)0.00095% CI0.000 - 0.000

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (mean), points	Reported bounds
Bexarotenen=16 Participants	-1.938	--4.861 - 0.986
Placebon=4 Participants	-6.500	--12.350 - -0.653

Mean Difference (Final Values)4.56395% CI-1.975 - 11.100p0.18t-test, 2 sided

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Change in NPI Scores in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change in NPI Scores in ALL Subjects From Baseline to Week 4

Time frame:Baseline to Week 4

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (mean), points	Reported bounds
Bexarotenen=16 Participants	-2.625	--6.783 - 1.533
Placebon=4 Participants	-2.250	--10.570 - 6.067

Mean Difference (Final Values)-0.37595% CI-9.674 - 8.924p0.94t-test, 2 sided

Amyloid biomarkers

16 endpoints

Primary/protocol endpoint

Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain

Time frame:Baseline to Week 4

change from baseline, improvement

Primary/protocol endpoint

Primary Outcome by Genotype (ALL SUBJECTS)

Time frame:Baseline to Week 4

change from baseline, improvement

Primary/protocol endpoint

Primary Outcome by Genotype (NON ApoE4 CARRIERS)

Time frame:Baseline to Week 4

descriptive

Primary/protocol endpoint

Primary Outcome by Genotype (ApoE4 CARRIERS)

Time frame:Baseline to Week 4

change from baseline, improvement

Primary/protocol endpoint

Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)

Time frame:Baseline to Week 4

change from baseline, improvement

Primary/protocol endpoint

Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)

Time frame:Baseline to Week 4

change from baseline, improvement

Primary/registry result

Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), SUVr	Reported bounds
Bexarotenen=16 Participants	-0.03	--0.06 - 0.01
Placebon=4 Participants	0.02	--0.05 - 0.10

Mean Difference (Final Values)-0.0595% CI-0.13 - 0.03p0.22t-test, 2 sided

Primary/registry result

Primary Outcome by Genotype (ALL SUBJECTS)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), SUVr	Reported bounds
BexaroteneFrontal Medial Orbitaln=16 Participants	-0.043	--0.081 - -0.006
Anterior Cingulaten=16 Participants	-0.040	--0.080 - 0.000
Parietaln=16 Participants	-0.003	--0.034 - 0.027
Posterior Cingulaten=16 Participants	-0.017	--0.065 - 0.031
Precuneusn=16 Participants	-0.027	--0.069 - 0.014
Temporaln=16 Participants	-0.038	--0.075 - 0.000
PlaceboFrontal Medial Orbitaln=4 Participants	-0.021	--0.096 - 0.054
Anterior Cingulaten=4 Participants	0.018	--0.061 - 0.098
Parietaln=4 Participants	0.044	--0.018 - 0.105
Posterior Cingulaten=4 Participants	0.044	--0.052 - 0.141
Precuneusn=4 Participants	0.040	--0.043 - 0.122
Temporaln=4 Participants	0.016	--0.059 - 0.090

Primary/registry result

Primary Outcome by Genotype (NON ApoE4 CARRIERS)

Time frame:Baseline to Week 4

descriptive

Posted result

Group	Value (mean), SUVr	Reported bounds
BexaroteneCompositen=4 Participants	-0.097	--0.155 - -0.040
Frontal Medial Orbitaln=4 Participants	-0.076	--0.146 - -0.007
Anterior Cingulaten=4 Participants	-0.096	--0.166 - -0.026
Parietaln=4 Participants	-0.068	--0.107 - -0.029
Posterior Cingulaten=4 Participants	-0.113	--0.180 - -0.046
Precuneusn=4 Participants	-0.127	--0.188 - -0.066
Temporaln=4 Participants	-0.104	--0.162 - -0.045
PlaceboCompositen=3 Participants	0.047	--0.019 - 0.114
Frontal Medial Orbitaln=3 Participants	0.005	--0.075 - 0.085
Anterior Cingulaten=3 Participants	0.048	--0.034 - 0.129
Parietaln=3 Participants	0.065	-0.020 - 0.110
Posterior Cingulaten=3 Participants	0.074	--0.004 - 0.151
Precuneusn=3 Participants	0.062	--0.008 - 0.132
Temporaln=3 Participants	0.031	--0.037 - 0.098

Primary/registry result

Primary Outcome by Genotype (ApoE4 CARRIERS)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), SUVr	Reported bounds
BexaroteneCompositen=12 Participants	-0.005	--0.041 - 0.031
Frontal Medial Orbitaln=12 Participants	-0.033	--0.074 - 0.009
Anterior Cingulaten=12 Participants	-0.022	--0.062 - 0.019
Parietaln=12 Participants	0.018	--0.013 - 0.050
Posterior Cingulaten=12 Participants	0.015	--0.035 - 0.065
Precuneusn=12 Participants	0.006	--0.031 - 0.043
Temporaln=12 Participants	-0.015	--0.055 - 0.024
PlaceboCompositen=1 Participants	-0.048	-NA - NA
Frontal Medial Orbitaln=1 Participants	-0.099	-NA - NA
Anterior Cingulaten=1 Participants	-0.069	-NA - NA
Parietaln=1 Participants	-0.019	-NA - NA
Posterior Cingulaten=1 Participants	-0.044	-NA - NA
Precuneusn=1 Participants	-0.027	-NA - NA
Temporaln=1 Participants	-0.030	-NA - NA

Primary/registry result

Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), SUVr	Reported bounds
BexaroteneCompositen=6 Participants	-0.015	--0.037 - 0.008
Frontal Medial Orbitaln=6 Participants	-0.061	--0.090 - -0.033
Anterior Cingulaten=6 Participants	-0.048	--0.080 - -0.016
Parietaln=6 Participants	0.034	-0.009 - 0.058
Posterior Cingulaten=6 Participants	-0.007	--0.035 - 0.022
Precuneusn=6 Participants	0.005	--0.021 - 0.032
Temporaln=6 Participants	-0.010	--0.041 - 0.020
PlaceboCompositen=1 Participants	-0.048	-NA - NA
Frontal Medial Orbitaln=1 Participants	-0.099	-NA - NA
Anterior Cingulaten=1 Participants	-0.069	-NA - NA
Parietaln=1 Participants	-0.019	-NA - NA
Posterior Cingulaten=1 Participants	-0.044	-NA - NA
Precuneusn=1 Participants	-0.027	-NA - NA
Temporaln=1 Participants	-0.030	-NA - NA

Primary/registry result

Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), SUVr	Reported bounds
BexaroteneCompositen=6 Participants	0.005	--0.066 - 0.075
Frontal Medial Orbitaln=6 Participants	-0.004	--0.077 - 0.069
Anterior Cingulaten=6 Participants	0.005	--0.067 - 0.077
Parietaln=6 Participants	0.003	--0.054 - 0.060
Posterior Cingulaten=6 Participants	0.037	--0.059 - 0.133
Precuneusn=6 Participants	0.006	--0.065 - 0.077
Temporaln=6 Participants	-0.020	--0.096 - 0.055

Secondary/protocol endpoint

Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/protocol endpoint

Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/registry result

Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Reported bounds
Bexarotenen=13 Participants	0.001	--0.007 - 0.008
Placebon=4 Participants	-0.005	--0.019 - 0.009

Mean Difference (Final Values)0.00695% CI-0.010 - 0.021p0.46t-test, 2 sided

Secondary/registry result

Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), ratio	Reported bounds
Bexarotenen=3 Participants	0.005	--0.016 - 0.026
Placebon=3 Participants	-0.005	--0.026 - 0.017

Mean Difference (Final Values)0.01095% CI-0.020 - 0.040p0.53t-test, 2 sided

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS)

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers)

Time frame:Baseline to Week 4

change from baseline, improvement

Secondary/registry result/low confidence

Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), pmol/L	Reported bounds
BexaroteneBeta Amyloid 40n=13 Participants	7.186	--3.673 - 18.045
Beta Amyloid 42n=13 Participants	0.585	--0.044 - 1.213
PlaceboBeta Amyloid 40n=4 Participants	-5.330	--24.910 - 14.246
Beta Amyloid 42n=4 Participants	-0.900	--2.033 - 0.233

Secondary/registry result/low confidence

Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers)

Time frame:Baseline to Week 4

change from baseline, improvement

Posted result

Group	Value (mean), pmol/L	Reported bounds
BexaroteneBeta Amyloid 40n=3 Participants	-3.503	--22.840 - 15.836
Beta Amyloid 42n=3 Participants	0.293	--0.873 - 1.460
PlaceboBeta Amyloid 40n=3 Participants	-8.550	--27.890 - 10.789
Beta Amyloid 42n=3 Participants	-1.127	--2.293 - 0.040

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Cummings JL, Zhong K, Kinney JW, Heaney C, Moll-Tudla J, Joshi A, Pontecorvo M, Devous M, Tang A, Bena J. Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer's disease. Alzheimers Res Ther. 2016 Jan 29;8:4. doi: 10.1186/s13195-016-0173-2.
PMID26822146via DERIVED

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.