Alzheimer's Disease
Conditions
Keywords
Mild to Moderate Alzheimer's Disease
Brief summary
Retinoid X receptors (RXR) are nuclear receptors that have been linked to numerous metabolic pathways relevant to Alzheimer's disease (AD) and Aβ (harmful protein) production and removal. The study drug bexarotene is an FDA approved anti-cancer agent but is not approved for use in Alzheimer's disease. Bexarotene acts as an RXR agonist that has reduced Aβ (harmful protein) in the brain in experimental models of Alzheimer's disease. This study aims to determine the safety and effect on abnormal proteins found in the brain (based on brain scans) of 300 mg of bexarotene administered for one month compared to placebo (inactive agent).
Interventions
DRUGBexarotene
Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
DRUGPlacebo
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain | Baseline to Week 4 | The primary study endpoint for all subjects is the change from baseline to Week 4 in amyloid burden as measured by standard uptake units regional (SUVr) on amyloid brain imaging obtained through 18F-AV-45 PET |
| Primary Outcome by Genotype (ALL SUBJECTS) | Baseline to Week 4 | This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (E-4 carriers compared to E-4 non-carriers) |
| Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Baseline to Week 4 | Measures changes from baseline on treatment compared to placebo at week 4 on composite and regional Beta Amyloid burden according to ApoE genotype (NON ApoE4 CARRIERS) |
| Primary Outcome by Genotype (ApoE4 CARRIERS) | Baseline to Week 4 | This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (E-4 carriers) |
| Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Baseline to Week 4 | This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (HETEROZYGOTE ApoE4 CARRIERS) |
| Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Baseline to Week 4 | This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (HOMOZYGOTE ApoE4 CARRIERS) There are no homozygote ApoE4 carriers on the placebo arm, therefore no data can be presented on this arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers) | Baseline to Week 4 | Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes (non ApoE4 carriers) |
| Change in MMSE Score in ALL Subjects From Baseline to Week 4 | Baseline to Week 4 | The MMSE evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. A lower score indicates more cognitive impairment. The lowest score that any particular person can get is 0 and the highest score is 30. |
| Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers | Baseline to Week 4 | This measures the change in the ratio of Beta Amyloid 42 to Beta Amyloid 40 from baseline to week 4 in non ApoE4 Carriers |
| Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects | Baseline to Week 4 | This measures the change in the ratio of Beta Amyloid 42 to Beta Amyloid 40 from baseline to week 4 in all subjects |
| Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4 | Baseline to Week 4 | The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 85 (worse). A positive change indicates cognitive worsening. |
| Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4 | Baseline to Week 4 | The CDR is a clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (CDR score of 0, 0.5, 1, 2, or 3, respectively). Higher score means more severe dementia rating. The score is based on interviews with the participant and study partner, using a structured interview that assesses six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. |
| Change in NPI Scores in ALL Subjects From Baseline to Week 4 | Baseline to Week 4 | The NPI is a well validated, reliable, multi-item instrument to assess psychopathology in AD based on interview with the study partner. The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score and the score for each subscale are the product of severity and frequency. Overall score range from 0 meaning no disturbance to 144 meaning severe disturbance |
| Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4 | Baseline to Week 4 | The ADCS-ADL is an activities-of-daily-living inventory developed by the ADCS to assess functional performance in participants with AD (Galasko et al., 1997). 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. Overall score range from 0 meaning fully independent to 78 meaning fully dependent on assistance for activities of daily living |
| Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS) | Baseline to Week 4 | Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes |
Countries
United States
Participant flow
Recruitment details
Recruitment was conducted in the United States at one site. The first participant was enrolled in April 2013.
Pre-assignment details
49 participants were screened, 29 were screen failures, 20 participants were randomized to treatment. 1 was withdrawn after Week 4 treatment. Inclusion and exclusion criteria was the strict basis for eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Bexarotene Treatment Arm 75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo | 16 |
| Placebo 1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo | 4 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Treatment Phase | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Bexarotene Treatment Arm | Total | Placebo |
|---|---|---|---|
| ADAS-Cog score | 49.9 units on a scale | 48.0 units on a scale | 40.3 units on a scale |
| ADCS-ADL score | 53.7 units on a scale | 55.9 units on a scale | 64.5 units on a scale |
| Age, Customized Age at Screening | 74.9 years STANDARD_DEVIATION 6.6 | 75.5 years STANDARD_DEVIATION 6.8 | 78.1 years STANDARD_DEVIATION 8 |
| ApoE4 Status Heterozygotes | 6 participants | 7 participants | 1 participants |
| ApoE4 Status Homozygotes | 6 participants | 6 participants | 0 participants |
| ApoE4 Status Non-carriers | 4 participants | 7 participants | 3 participants |
| CDR score | 1.4 units on a scale | 1.4 units on a scale | 1.1 units on a scale |
| MMSE total score | 13.7 units on a scale | 14.4 units on a scale | 17.0 units on a scale |
| NPI Distress Score | 6.5 units on a scale | 6.1 units on a scale | 4.3 units on a scale |
| NPI score | 8.7 units on a scale | 8.4 units on a scale | 7.0 units on a scale |
| Race/Ethnicity, Customized Race - African American | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Race - Caucasian | 15 participants | 19 participants | 4 participants |
| Sex: Female, Male Female | 10 Participants | 13 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 1 Participants |
| Years of Cognitive Symptoms | 4.6 years STANDARD_DEVIATION 1.9 | 4.3 years STANDARD_DEVIATION 1.9 | 2.8 years STANDARD_DEVIATION 0.96 |
| Years of Education | 14.7 years STANDARD_DEVIATION 4.9 | 14.2 years STANDARD_DEVIATION 4.7 | 12.3 years STANDARD_DEVIATION 3.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 16 | 0 / 4 |
| serious Total, serious adverse events | 0 / 16 | 0 / 4 |
Outcome results
Primary
Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain
The primary study endpoint for all subjects is the change from baseline to Week 4 in amyloid burden as measured by standard uptake units regional (SUVr) on amyloid brain imaging obtained through 18F-AV-45 PET
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain | -0.03 SUVr |
| Placebo | Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain | 0.02 SUVr |
p-value: 0.2295% CI: [-0.13, 0.03]t-test, 2 sided
Primary
Primary Outcome by Genotype (ALL SUBJECTS)
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (E-4 carriers compared to E-4 non-carriers)
Time frame: Baseline to Week 4
Population: Change om composite and regional Beta Amyloid burden according to ApoE genotype on ALL SUBJECTS
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexarotene | Primary Outcome by Genotype (ALL SUBJECTS) | Frontal Medial Orbital | -0.043 SUVr |
| Bexarotene | Primary Outcome by Genotype (ALL SUBJECTS) | Anterior Cingulate | -0.040 SUVr |
| Bexarotene | Primary Outcome by Genotype (ALL SUBJECTS) | Parietal | -0.003 SUVr |
| Bexarotene | Primary Outcome by Genotype (ALL SUBJECTS) | Posterior Cingulate | -0.017 SUVr |
| Bexarotene | Primary Outcome by Genotype (ALL SUBJECTS) | Precuneus | -0.027 SUVr |
| Bexarotene | Primary Outcome by Genotype (ALL SUBJECTS) | Temporal | -0.038 SUVr |
| Placebo | Primary Outcome by Genotype (ALL SUBJECTS) | Precuneus | 0.040 SUVr |
| Placebo | Primary Outcome by Genotype (ALL SUBJECTS) | Frontal Medial Orbital | -0.021 SUVr |
| Placebo | Primary Outcome by Genotype (ALL SUBJECTS) | Posterior Cingulate | 0.044 SUVr |
| Placebo | Primary Outcome by Genotype (ALL SUBJECTS) | Anterior Cingulate | 0.018 SUVr |
| Placebo | Primary Outcome by Genotype (ALL SUBJECTS) | Temporal | 0.016 SUVr |
| Placebo | Primary Outcome by Genotype (ALL SUBJECTS) | Parietal | 0.044 SUVr |
Primary
Primary Outcome by Genotype (ApoE4 CARRIERS)
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (E-4 carriers)
Time frame: Baseline to Week 4
Population: Change in composite and regional Beta Amyloid burden on ApoE4 carriers
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexarotene | Primary Outcome by Genotype (ApoE4 CARRIERS) | Composite | -0.005 SUVr |
| Bexarotene | Primary Outcome by Genotype (ApoE4 CARRIERS) | Anterior Cingulate | -0.022 SUVr |
| Bexarotene | Primary Outcome by Genotype (ApoE4 CARRIERS) | Precuneus | 0.006 SUVr |
| Bexarotene | Primary Outcome by Genotype (ApoE4 CARRIERS) | Parietal | 0.018 SUVr |
| Bexarotene | Primary Outcome by Genotype (ApoE4 CARRIERS) | Frontal Medial Orbital | -0.033 SUVr |
| Bexarotene | Primary Outcome by Genotype (ApoE4 CARRIERS) | Temporal | -0.015 SUVr |
| Bexarotene | Primary Outcome by Genotype (ApoE4 CARRIERS) | Posterior Cingulate | 0.015 SUVr |
| Placebo | Primary Outcome by Genotype (ApoE4 CARRIERS) | Temporal | -0.030 SUVr |
| Placebo | Primary Outcome by Genotype (ApoE4 CARRIERS) | Posterior Cingulate | -0.044 SUVr |
| Placebo | Primary Outcome by Genotype (ApoE4 CARRIERS) | Precuneus | -0.027 SUVr |
| Placebo | Primary Outcome by Genotype (ApoE4 CARRIERS) | Composite | -0.048 SUVr |
| Placebo | Primary Outcome by Genotype (ApoE4 CARRIERS) | Frontal Medial Orbital | -0.099 SUVr |
| Placebo | Primary Outcome by Genotype (ApoE4 CARRIERS) | Anterior Cingulate | -0.069 SUVr |
| Placebo | Primary Outcome by Genotype (ApoE4 CARRIERS) | Parietal | -0.019 SUVr |
Primary
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (HETEROZYGOTE ApoE4 CARRIERS)
Time frame: Baseline to Week 4
Population: Change in composite and regional Beta Amyloid burden on Heterozygote ApoE4 carriers
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexarotene | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Anterior Cingulate | -0.048 SUVr |
| Bexarotene | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Posterior Cingulate | -0.007 SUVr |
| Bexarotene | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Frontal Medial Orbital | -0.061 SUVr |
| Bexarotene | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Precuneus | 0.005 SUVr |
| Bexarotene | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Parietal | 0.034 SUVr |
| Bexarotene | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Temporal | -0.010 SUVr |
| Bexarotene | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Composite | -0.015 SUVr |
| Placebo | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Temporal | -0.030 SUVr |
| Placebo | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Composite | -0.048 SUVr |
| Placebo | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Frontal Medial Orbital | -0.099 SUVr |
| Placebo | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Anterior Cingulate | -0.069 SUVr |
| Placebo | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Parietal | -0.019 SUVr |
| Placebo | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Posterior Cingulate | -0.044 SUVr |
| Placebo | Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS) | Precuneus | -0.027 SUVr |
Primary
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (HOMOZYGOTE ApoE4 CARRIERS) There are no homozygote ApoE4 carriers on the placebo arm, therefore no data can be presented on this arm.
Time frame: Baseline to Week 4
Population: Change in composite and regional Beta Amyloid burden on Homozygote ApoE4 carriers.~There are no homozygote ApoE4 carriers on the placebo arm, therefore no data can be presented on this arm.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexarotene | Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Composite | 0.005 SUVr |
| Bexarotene | Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Frontal Medial Orbital | -0.004 SUVr |
| Bexarotene | Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Anterior Cingulate | 0.005 SUVr |
| Bexarotene | Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Parietal | 0.003 SUVr |
| Bexarotene | Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Posterior Cingulate | 0.037 SUVr |
| Bexarotene | Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Precuneus | 0.006 SUVr |
| Bexarotene | Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS) | Temporal | -0.020 SUVr |
Primary
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Measures changes from baseline on treatment compared to placebo at week 4 on composite and regional Beta Amyloid burden according to ApoE genotype (NON ApoE4 CARRIERS)
Time frame: Baseline to Week 4
Population: Change in composite and regional Beta Amyloid Burden on non-ApoE4 carriers
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexarotene | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Composite | -0.097 SUVr |
| Bexarotene | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Posterior Cingulate | -0.113 SUVr |
| Bexarotene | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Anterior Cingulate | -0.096 SUVr |
| Bexarotene | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Precuneus | -0.127 SUVr |
| Bexarotene | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Frontal Medial Orbital | -0.076 SUVr |
| Bexarotene | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Temporal | -0.104 SUVr |
| Bexarotene | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Parietal | -0.068 SUVr |
| Placebo | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Temporal | 0.031 SUVr |
| Placebo | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Composite | 0.047 SUVr |
| Placebo | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Frontal Medial Orbital | 0.005 SUVr |
| Placebo | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Anterior Cingulate | 0.048 SUVr |
| Placebo | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Parietal | 0.065 SUVr |
| Placebo | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Posterior Cingulate | 0.074 SUVr |
| Placebo | Primary Outcome by Genotype (NON ApoE4 CARRIERS) | Precuneus | 0.062 SUVr |
Secondary
Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4
The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 85 (worse). A positive change indicates cognitive worsening.
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4 | 0.375 points |
| Placebo | Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4 | -0.250 points |
p-value: 0.8395% CI: [-5.029, 6.279]t-test, 2 sided
Secondary
Change in MMSE Score in ALL Subjects From Baseline to Week 4
The MMSE evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. A lower score indicates more cognitive impairment. The lowest score that any particular person can get is 0 and the highest score is 30.
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Change in MMSE Score in ALL Subjects From Baseline to Week 4 | 0.750 points |
| Placebo | Change in MMSE Score in ALL Subjects From Baseline to Week 4 | 1.750 points |
p-value: 0.5795% CI: [-4.428, 2.428]t-test, 2 sided
Secondary
Change in NPI Scores in ALL Subjects From Baseline to Week 4
The NPI is a well validated, reliable, multi-item instrument to assess psychopathology in AD based on interview with the study partner. The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score and the score for each subscale are the product of severity and frequency. Overall score range from 0 meaning no disturbance to 144 meaning severe disturbance
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Change in NPI Scores in ALL Subjects From Baseline to Week 4 | -2.625 points |
| Placebo | Change in NPI Scores in ALL Subjects From Baseline to Week 4 | -2.250 points |
p-value: 0.9495% CI: [-9.674, 8.924]t-test, 2 sided
Secondary
Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4
The ADCS-ADL is an activities-of-daily-living inventory developed by the ADCS to assess functional performance in participants with AD (Galasko et al., 1997). 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. Overall score range from 0 meaning fully independent to 78 meaning fully dependent on assistance for activities of daily living
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4 | -1.938 points |
| Placebo | Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4 | -6.500 points |
p-value: 0.1895% CI: [-1.975, 11.1]t-test, 2 sided
Secondary
Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4
The CDR is a clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (CDR score of 0, 0.5, 1, 2, or 3, respectively). Higher score means more severe dementia rating. The score is based on interviews with the participant and study partner, using a structured interview that assesses six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
Time frame: Baseline to Week 4
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4 | 0.000 units on a scale |
| Placebo | Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4 | 0.000 units on a scale |
95% CI: [0, 0]
Secondary
Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects
This measures the change in the ratio of Beta Amyloid 42 to Beta Amyloid 40 from baseline to week 4 in all subjects
Time frame: Baseline to Week 4
Population: There were only a total of 17 subjects who were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 3 subjects were unsuccessful.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects | 0.001 ratio |
| Placebo | Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects | -0.005 ratio |
p-value: 0.4695% CI: [-0.01, 0.021]t-test, 2 sided
Secondary
Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers
This measures the change in the ratio of Beta Amyloid 42 to Beta Amyloid 40 from baseline to week 4 in non ApoE4 Carriers
Time frame: Baseline to Week 4
Population: Of the 7 total subjects who were non-ApoE carriers, only 6 subjects were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 1 subject were unsuccessful.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Bexarotene | Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers | 0.005 ratio |
| Placebo | Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers | -0.005 ratio |
p-value: 0.5395% CI: [-0.02, 0.04]t-test, 2 sided
Secondary
Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS)
Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes
Time frame: Baseline to Week 4
Population: Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes in ALL SUBJECTS. There were only a total of 17 subjects who were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 3 subjects were unsuccessful.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexarotene | Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS) | Beta Amyloid 40 | 7.186 pmol/L |
| Bexarotene | Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS) | Beta Amyloid 42 | 0.585 pmol/L |
| Placebo | Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS) | Beta Amyloid 40 | -5.330 pmol/L |
| Placebo | Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS) | Beta Amyloid 42 | -0.900 pmol/L |
Secondary
Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers)
Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes (non ApoE4 carriers)
Time frame: Baseline to Week 4
Population: Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels in non ApoE4 carriers. Of the 7 total subjects who were non-ApoE carriers, only 6 subjects were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 1 subject were unsuccessful.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bexarotene | Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers) | Beta Amyloid 40 | -3.503 pmol/L |
| Bexarotene | Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers) | Beta Amyloid 42 | 0.293 pmol/L |
| Placebo | Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers) | Beta Amyloid 40 | -8.550 pmol/L |
| Placebo | Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers) | Beta Amyloid 42 | -1.127 pmol/L |