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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01782742
First received: January 29, 2013
Last updated: February 10, 2016
Last verified: February 2016
Results First Received: February 10, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: Bexarotene
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was conducted in the United States at one site. The first participant was enrolled in April 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
49 participants were screened, 29 were screen failures, 20 participants were randomized to treatment. 1 was withdrawn after Week 4 treatment.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.

Reporting Groups
  Description
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

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


Participant Flow for 2 periods

Period 1:   Double-blind Treatment Phase
    Bexarotene Treatment Arm     Placebo  
STARTED     16     4  
COMPLETED     15     4  
NOT COMPLETED     1     0  
Adverse Event                 1                 0  

Period 2:   Open Label Phase
    Bexarotene Treatment Arm     Placebo  
STARTED     19     0  
COMPLETED     19     0  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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

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 Total of all reporting groups

Baseline Measures
    Bexarotene Treatment Arm     Placebo     Total  
Number of Participants  
[units: participants]
  16     4     20  
Age, Customized [1]
[units: years]
Mean (Standard Deviation)
     
Age at Screening     74.9  (6.6)     78.1  (8.0)     75.5  (6.8)  
Gender  
[units: participants]
     
Female     10     3     13  
Male     6     1     7  
Race/Ethnicity, Customized  
[units: participants]
     
Race - Caucasian     15     4     19  
Race - African American     1     0     1  
Years of Education  
[units: years]
Mean (Standard Deviation)
  14.7  (4.9)     12.3  (3.3)     14.2  (4.7)  
Years of Cognitive Symptoms  
[units: years]
Mean (Standard Deviation)
  4.6  (1.9)     2.8  (0.96)     4.3  (1.9)  
MMSE total score [2]
[units: units on a scale]
Mean (Full Range)
  13.7  
  (8 to 23)  
  17.0  
  (11 to 23)  
  14.4  
  (8 to 23)  
ADAS-Cog score [3]
[units: units on a scale]
Mean (Full Range)
  49.9  
  (35 to 65)  
  40.3  
  (28 to 54)  
  48.0  
  (28 to 65)  
CDR score [4]
[units: units on a scale]
Mean (Full Range)
  1.4  
  (0 to 2)  
  1.1  
  (0 to 2)  
  1.4  
  (0 to 2)  
NPI score [5]
[units: units on a scale]
Mean (Full Range)
  8.7  
  (0 to 29)  
  7.0  
  (2 to 16)  
  8.4  
  (0 to 29)  
NPI Distress Score [6]
[units: units on a scale]
Mean (Full Range)
  6.5  
  (0 to 35)  
  4.3  
  (2 to 6)  
  6.1  
  (0 to 35)  
ADCS-ADL score [7]
[units: units on a scale]
Mean (Full Range)
  53.7  
  (34 to 77)  
  64.5  
  (37 to 76)  
  55.9  
  (34 to 77)  
ApoE4 Status  
[units: participants]
     
Non-carriers     4     3     7  
Heterozygotes     6     1     7  
Homozygotes     6     0     6  
[1] Age at Screening
[2] 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.
[3] 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.
[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.
[5] 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.
[6] 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.
[7] 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.



  Outcome Measures
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1.  Primary:   Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain   [ Time Frame: Baseline to Week 4 ]

2.  Primary:   Primary Outcome by Genotype (ALL SUBJECTS)   [ Time Frame: Baseline to Week 4 ]

3.  Primary:   Primary Outcome by Genotype (NON ApoE4 CARRIERS)   [ Time Frame: Baseline to Week 4 ]

4.  Primary:   Primary Outcome by Genotype (ApoE4 CARRIERS)   [ Time Frame: Baseline to Week 4 ]

5.  Primary:   Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)   [ Time Frame: Baseline to Week 4 ]

6.  Primary:   Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)   [ Time Frame: Baseline to Week 4 ]

7.  Secondary:   Change in MMSE Score in ALL Subjects From Baseline to Week 4   [ Time Frame: Baseline to Week 4 ]

8.  Secondary:   Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4   [ Time Frame: Baseline to Week 4 ]

9.  Secondary:   Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4   [ Time Frame: Baseline to Week 4 ]

10.  Secondary:   Change in NPI Scores in ALL Subjects From Baseline to Week 4   [ Time Frame: Baseline to Week 4 ]

11.  Secondary:   Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4   [ Time Frame: Baseline to Week 4 ]

12.  Secondary:   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 ]

13.  Secondary:   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 ]

14.  Secondary:   Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects   [ Time Frame: Baseline to Week 4 ]

15.  Secondary:   Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers   [ Time Frame: Baseline to Week 4 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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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
e-mail: cumminj@ccf.org


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01782742     History of Changes
Other Study ID Numbers: CCF-IRB 12-783
Study First Received: January 29, 2013
Results First Received: February 10, 2016
Last Updated: February 10, 2016
Health Authority: United States: Institutional Review Board