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Bexarotene Amyloid Treatment for Alzheimer's Disease (BEAT-AD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01782742
Recruitment Status : Completed
First Posted : February 4, 2013
Results First Posted : February 12, 2016
Last Update Posted : February 12, 2016
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: Bexarotene
Drug: Placebo
Enrollment 20
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Details 49 participants were screened, 29 were screen failures, 20 participants were randomized to treatment. 1 was withdrawn after Week 4 treatment.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.
Arm/Group Title Bexarotene Treatment Arm Placebo
Hide Arm/Group Description

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

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

Period Title: Double-blind Treatment Phase
Started 16 4
Completed 15 4
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Period Title: Open Label Phase
Started 19 0
Completed 19 0
Not Completed 0 0
Arm/Group Title Bexarotene Treatment Arm Placebo Total
Hide Arm/Group Description

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

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

Total of all reporting groups
Overall Number of Baseline Participants 16 4 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Age at Screening Number Analyzed 16 participants 4 participants 20 participants
74.9  (6.6) 78.1  (8.0) 75.5  (6.8)
[1]
Measure Description: Age at Screening
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 4 participants 20 participants
Female
10
  62.5%
3
  75.0%
13
  65.0%
Male
6
  37.5%
1
  25.0%
7
  35.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 4 participants 20 participants
Race - Caucasian 15 4 19
Race - African American 1 0 1
Years of Education  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 4 participants 20 participants
14.7  (4.9) 12.3  (3.3) 14.2  (4.7)
Years of Cognitive Symptoms  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 4 participants 20 participants
4.6  (1.9) 2.8  (0.96) 4.3  (1.9)
MMSE total score   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 4 participants 20 participants
13.7
(8 to 23)
17.0
(11 to 23)
14.4
(8 to 23)
[1]
Measure Description: 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.
ADAS-Cog score   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 4 participants 20 participants
49.9
(35 to 65)
40.3
(28 to 54)
48.0
(28 to 65)
[1]
Measure Description: 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.
CDR score   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 4 participants 20 participants
1.4
(0 to 2)
1.1
(0 to 2)
1.4
(0 to 2)
[1]
Measure Description: 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.
NPI score   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 4 participants 20 participants
8.7
(0 to 29)
7.0
(2 to 16)
8.4
(0 to 29)
[1]
Measure Description: 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.
NPI Distress Score   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 4 participants 20 participants
6.5
(0 to 35)
4.3
(2 to 6)
6.1
(0 to 35)
[1]
Measure Description: NPI distress score measures the distress that the caregiver experiences during the previous 4 weeks from the assessment date. Distress score is measured on a scale between 0 to 5. 0 being not at all distressed to 5 very severely or extremely distressed. The scores for all 12 domains are added up becomes the total score. 0 means no caregiver distress and 60 means extreme caregiver distress.
ADCS-ADL score   [1] 
Mean (Full Range)
Unit of measure:  Units on a scale
Number Analyzed 16 participants 4 participants 20 participants
53.7
(34 to 77)
64.5
(37 to 76)
55.9
(34 to 77)
[1]
Measure Description: 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.
ApoE4 Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants 4 participants 20 participants
Non-carriers 4 3 7
Heterozygotes 6 1 7
Homozygotes 6 0 6
1.Primary Outcome
Title Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 16 4
Mean (95% Confidence Interval)
Unit of Measure: SUVr
-0.03
(-0.06 to 0.01)
0.02
(-0.05 to 0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.13 to 0.03
Estimation Comments [Not Specified]
2.Primary Outcome
Title Primary Outcome by Genotype (ALL SUBJECTS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Change om composite and regional Beta Amyloid burden according to ApoE genotype on ALL SUBJECTS
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 16 4
Mean (95% Confidence Interval)
Unit of Measure: SUVr
Frontal Medial Orbital
-0.043
(-0.081 to -0.006)
-0.021
(-0.096 to 0.054)
Anterior Cingulate
-0.040
(-0.080 to 0.000)
0.018
(-0.061 to 0.098)
Parietal
-0.003
(-0.034 to 0.027)
0.044
(-0.018 to 0.105)
Posterior Cingulate
-0.017
(-0.065 to 0.031)
0.044
(-0.052 to 0.141)
Precuneus
-0.027
(-0.069 to 0.014)
0.040
(-0.043 to 0.122)
Temporal
-0.038
(-0.075 to 0.000)
0.016
(-0.059 to 0.090)
3.Primary Outcome
Title Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Change in composite and regional Beta Amyloid Burden on non-ApoE4 carriers
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 4 3
Mean (95% Confidence Interval)
Unit of Measure: SUVr
Composite
-0.097
(-0.155 to -0.040)
0.047
(-0.019 to 0.114)
Frontal Medial Orbital
-0.076
(-0.146 to -0.007)
0.005
(-0.075 to 0.085)
Anterior Cingulate
-0.096
(-0.166 to -0.026)
0.048
(-0.034 to 0.129)
Parietal
-0.068
(-0.107 to -0.029)
0.065
(0.020 to 0.110)
Posterior Cingulate
-0.113
(-0.180 to -0.046)
0.074
(-0.004 to 0.151)
Precuneus
-0.127
(-0.188 to -0.066)
0.062
(-0.008 to 0.132)
Temporal
-0.104
(-0.162 to -0.045)
0.031
(-0.037 to 0.098)
4.Primary Outcome
Title Primary Outcome by Genotype (ApoE4 CARRIERS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Change in composite and regional Beta Amyloid burden on ApoE4 carriers
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 12 1
Mean (95% Confidence Interval)
Unit of Measure: SUVr
Composite
-0.005
(-0.041 to 0.031)
-0.048 [1] 
(NA to NA)
Frontal Medial Orbital
-0.033
(-0.074 to 0.009)
-0.099 [1] 
(NA to NA)
Anterior Cingulate
-0.022
(-0.062 to 0.019)
-0.069 [1] 
(NA to NA)
Parietal
0.018
(-0.013 to 0.050)
-0.019 [1] 
(NA to NA)
Posterior Cingulate
0.015
(-0.035 to 0.065)
-0.044 [1] 
(NA to NA)
Precuneus
0.006
(-0.031 to 0.043)
-0.027 [1] 
(NA to NA)
Temporal
-0.015
(-0.055 to 0.024)
-0.030 [1] 
(NA to NA)
[1]
With 1 placebo patient, variability within the group cannot measured effectively
5.Primary Outcome
Title Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Change in composite and regional Beta Amyloid burden on Heterozygote ApoE4 carriers
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 6 1
Mean (95% Confidence Interval)
Unit of Measure: SUVr
Composite
-0.015
(-0.037 to 0.008)
-0.048 [1] 
(NA to NA)
Frontal Medial Orbital
-0.061
(-0.090 to -0.033)
-0.099 [1] 
(NA to NA)
Anterior Cingulate
-0.048
(-0.080 to -0.016)
-0.069 [1] 
(NA to NA)
Parietal
0.034
(0.009 to 0.058)
-0.019 [1] 
(NA to NA)
Posterior Cingulate
-0.007
(-0.035 to 0.022)
-0.044 [1] 
(NA to NA)
Precuneus
0.005
(-0.021 to 0.032)
-0.027 [1] 
(NA to NA)
Temporal
-0.010
(-0.041 to 0.020)
-0.030 [1] 
(NA to NA)
[1]
With 1 placebo patient, variability within the group cannot measured effectively
6.Primary Outcome
Title Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description

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/Group Title Bexarotene
Hide Arm/Group Description:

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

Overall Number of Participants Analyzed 6
Mean (95% Confidence Interval)
Unit of Measure: SUVr
Composite
0.005
(-0.066 to 0.075)
Frontal Medial Orbital
-0.004
(-0.077 to 0.069)
Anterior Cingulate
0.005
(-0.067 to 0.077)
Parietal
0.003
(-0.054 to 0.060)
Posterior Cingulate
0.037
(-0.059 to 0.133)
Precuneus
0.006
(-0.065 to 0.077)
Temporal
-0.020
(-0.096 to 0.055)
7.Secondary Outcome
Title Change in MMSE Score in ALL Subjects From Baseline to Week 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 16 4
Mean (95% Confidence Interval)
Unit of Measure: points
0.750
(-0.783 to 2.283)
1.750
(-1.316 to 4.816)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.000
Confidence Interval (2-Sided) 95%
-4.428 to 2.428
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 16 4
Mean (95% Confidence Interval)
Unit of Measure: points
0.375
(-2.153 to 2.903)
-0.250
(-5.307 to 4.807)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.83
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.625
Confidence Interval (2-Sided) 95%
-5.029 to 6.279
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 16 4
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.000
(0.000 to 0.000)
0.000
(0.000 to 0.000)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.000
Confidence Interval (2-Sided) 95%
0.000 to 0.000
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in NPI Scores in ALL Subjects From Baseline to Week 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 16 4
Mean (95% Confidence Interval)
Unit of Measure: points
-2.625
(-6.783 to 1.533)
-2.250
(-10.570 to 6.067)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.94
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.375
Confidence Interval (2-Sided) 95%
-9.674 to 8.924
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 16 4
Mean (95% Confidence Interval)
Unit of Measure: points
-1.938
(-4.861 to 0.986)
-6.500
(-12.350 to -0.653)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.563
Confidence Interval (2-Sided) 95%
-1.975 to 11.100
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 13 4
Mean (95% Confidence Interval)
Unit of Measure: pmol/L
Beta Amyloid 40
7.186
(-3.673 to 18.045)
-5.330
(-24.910 to 14.246)
Beta Amyloid 42
0.585
(-0.044 to 1.213)
-0.900
(-2.033 to 0.233)
13.Secondary Outcome
Title Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 3 3
Mean (95% Confidence Interval)
Unit of Measure: pmol/L
Beta Amyloid 40
-3.503
(-22.840 to 15.836)
-8.550
(-27.890 to 10.789)
Beta Amyloid 42
0.293
(-0.873 to 1.460)
-1.127
(-2.293 to 0.040)
14.Secondary Outcome
Title Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 13 4
Mean (95% Confidence Interval)
Unit of Measure: ratio
0.001
(-0.007 to 0.008)
-0.005
(-0.019 to 0.009)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.006
Confidence Interval (2-Sided) 95%
-0.010 to 0.021
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Bexarotene Placebo
Hide Arm/Group Description:

75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.

Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo

1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Overall Number of Participants Analyzed 3 3
Mean (95% Confidence Interval)
Unit of Measure: ratio
0.005
(-0.016 to 0.026)
-0.005
(-0.026 to 0.017)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bexarotene, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.53
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.010
Confidence Interval (2-Sided) 95%
-0.020 to 0.040
Estimation Comments [Not Specified]
Time Frame Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bexarotene Treatment Arm Placebo
Hide Arm/Group Description

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

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

All-Cause Mortality
Bexarotene Treatment Arm Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Bexarotene Treatment Arm Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      0/4 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Bexarotene Treatment Arm Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/16 (87.50%)      0/4 (0.00%)    
Gastrointestinal disorders     
Elevated cholesterol level   6/16 (37.50%)  6 0/4 (0.00%)  0
Hepatobiliary disorders     
Elevated triglyceride levels   13/16 (81.25%)  13 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dry cough   1/16 (6.25%)  1 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders     
Blister on toe  [1]  1/16 (6.25%)  1 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Participant had a blister on 2nd toe of left foot
Sample size of this trial is small. There was 1 participant withdrawal due to adverse event. Primary outcome measures were completed by all 20 participants as anticipated.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Jeffrey Cummings, MD, ScD
Organization: Cleveland Clinic Lou Ruvo Center for Brain Health
Phone: 702.483.6029
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01782742     History of Changes
Other Study ID Numbers: CCF-IRB 12-783
First Submitted: January 29, 2013
First Posted: February 4, 2013
Results First Submitted: February 10, 2016
Results First Posted: February 12, 2016
Last Update Posted: February 12, 2016