Trial Outcomes & Findings for Trial of Carvedilol in Alzheimer's Disease (NCT NCT01354444)

Last Updated: 2018-02-06

Results Overview

The investigators measured episodic memory (as evidence by the Hopkins Verbal Learning Test (HVLT)) before and after 6 months randomized placebo-controlled double-blind treatment with carvedilol at a target dose of 25 mg daily. Changes in HVLT Immediate and Delayed Recall score in 14 Alzheimer's Disease (AD) participants taking carvedilol vs. 15 AD participants taking placebo were compared. HVLT test score ranges are as follows: immediate recall (0-24) delayed recall (0-12). Higher scores indicate better episodic memory recall.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

29 participants

Primary outcome timeframe

Baseline, 3 months, and 6 months

Results posted on

2018-02-06

Participant Flow

Participant milestones

Participant milestones
Measure	Carvedilol Carvedilol is a is a beta-blocker. Beta-blockers are generally used to reduce the workload on the heart and help it to beat more regularly. Carvedilol: target dose of 25 mg daily which is half the maximum dose used in clinical practice	Placebo Non active substance Placebo: a pill that will look like the active drug but will not contain any carvedilol
Overall Study STARTED	14	15
Overall Study COMPLETED	6	11
Overall Study NOT COMPLETED	8	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Carvedilol in Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carvedilol n=14 Participants Carvedilol is a is a beta-blocker. Beta-blockers are generally used to reduce the workload on the heart and help it to beat more regularly. Carvedilol: target dose of 25 mg daily which is half the maximum dose used in clinical practice	Placebo n=15 Participants Non active substance Placebo: a pill that will look like the active drug but will not contain any carvedilol	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 3 months, and 6 months

Outcome measures

Outcome measures
Measure	HVLT Score in Placebo Group n=15 Participants Descriptive statistics for immediate recall in the Hopkins Verbal Learning Test in the placebo group	HVLT Score in Treatment Group n=14 Participants Descriptive statistics for immediate recall in the Hopkins Verbal Learning Test in the treatment group
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months HVLT score at Baseline (immediate recall)	13 Scores on a scale Standard Deviation 4	12 Scores on a scale Standard Deviation 6
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months HVLT score at 3 months (immediate recall)	12 Scores on a scale Standard Deviation 5	13 Scores on a scale Standard Deviation 4
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months HVLT score at 6 months (immediate recall)	12 Scores on a scale Standard Deviation 5	13 Scores on a scale Standard Deviation 6
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months HVLT score at Baseline (delayed recall)	1 Scores on a scale Standard Deviation 2	1 Scores on a scale Standard Deviation 1
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months HVLT score at 3 months (delayed recall)	1 Scores on a scale Standard Deviation 2	1 Scores on a scale Standard Deviation 2
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months HVLT score at 6 months (delayed recall)	1 Scores on a scale Standard Deviation 2	0 Scores on a scale Standard Deviation 0

SECONDARY outcome

Timeframe: 6 months

The investigators will measure CSF Abeta oligomer levels before and after 6 months randomized placebo-controlled double-blind treatment with carvedilol at a target dose of 25 mg daily, comparing the change in levels in 6 AD participants taking carvedilol vs. 10 AD participants taking placebo. These 16 participants had both baseline and 6 month CSF collected (of the entire study population). CSF was collected at the baseline visit and 6 months later.

Outcome measures

Outcome measures
Measure	HVLT Score in Placebo Group n=6 Participants Descriptive statistics for immediate recall in the Hopkins Verbal Learning Test in the placebo group	HVLT Score in Treatment Group n=10 Participants Descriptive statistics for immediate recall in the Hopkins Verbal Learning Test in the treatment group
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Baseline Tau (pg/mL)	169.476 pg/mL Standard Deviation 93.931	169.484 pg/mL Standard Deviation 48.386
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Baseline ABeta42 (pg/mL)	396.985 pg/mL Standard Deviation 212.411	379.406 pg/mL Standard Deviation 100.892
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Baseline P tau (pg/mL)	42.666 pg/mL Standard Deviation 10.176	66.133 pg/mL Standard Deviation 24.503
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Six month Tau (pg/mL)	222.461 pg/mL Standard Deviation 139.839	171.757 pg/mL Standard Deviation 53.72
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Six month ABeta42 (pg/mL)	499.325 pg/mL Standard Deviation 174.308	361.563 pg/mL Standard Deviation 89.044
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Six month P tau (pg/mL)	56.003 pg/mL Standard Deviation 23.984	64.331 pg/mL Standard Deviation 25.766

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	HVLT Score in Placebo Group n=6 Participants Descriptive statistics for immediate recall in the Hopkins Verbal Learning Test in the placebo group	HVLT Score in Treatment Group n=10 Participants Descriptive statistics for immediate recall in the Hopkins Verbal Learning Test in the treatment group
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Baseline Oligomeric ABeta (ng/mL)	3.83 ng/mL Standard Deviation 3.314	0.129 ng/mL Standard Deviation 0.034
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers Six month oligomeric ABeta (ng/mL)	3.895 ng/mL Standard Deviation 3.376	0.117 ng/mL Standard Deviation 0.101

Adverse Events

Carvedilol

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Carvedilol n=14 participants at risk Carvedilol is a is a beta-blocker. Beta-blockers are generally used to reduce the workload on the heart and help it to beat more regularly. Carvedilol: target dose of 25 mg daily which is half the maximum dose used in clinical practice	Placebo n=15 participants at risk Non active substance Placebo: a pill that will look like the active drug but will not contain any carvedilol
Blood and lymphatic system disorders HEME	7.1% 1/14 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.	0.00% 0/15 Adverse Events are presented without regard to the specific Adverse Event Term.
Gastrointestinal disorders GI	0.00% 0/14 Adverse Events are presented without regard to the specific Adverse Event Term.	6.7% 1/15 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.
Nervous system disorders Neurologic	7.1% 1/14 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.	0.00% 0/15 Adverse Events are presented without regard to the specific Adverse Event Term.

Other adverse events

Other adverse events
Measure	Carvedilol n=14 participants at risk Carvedilol is a is a beta-blocker. Beta-blockers are generally used to reduce the workload on the heart and help it to beat more regularly. Carvedilol: target dose of 25 mg daily which is half the maximum dose used in clinical practice	Placebo n=15 participants at risk Non active substance Placebo: a pill that will look like the active drug but will not contain any carvedilol
Blood and lymphatic system disorders HEME	7.1% 1/14 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.	6.7% 1/15 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.
Cardiac disorders Cardiac	71.4% 10/14 • Number of events 10 Adverse Events are presented without regard to the specific Adverse Event Term.	66.7% 10/15 • Number of events 10 Adverse Events are presented without regard to the specific Adverse Event Term.
Nervous system disorders Systemic	14.3% 2/14 • Number of events 2 Adverse Events are presented without regard to the specific Adverse Event Term.	26.7% 4/15 • Number of events 4 Adverse Events are presented without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Dermatologic	0.00% 0/14 Adverse Events are presented without regard to the specific Adverse Event Term.	6.7% 1/15 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.
Psychiatric disorders Psychiatric	7.1% 1/14 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.	33.3% 5/15 • Number of events 5 Adverse Events are presented without regard to the specific Adverse Event Term.
Gastrointestinal disorders GI	14.3% 2/14 • Number of events 2 Adverse Events are presented without regard to the specific Adverse Event Term.	20.0% 3/15 • Number of events 3 Adverse Events are presented without regard to the specific Adverse Event Term.
Nervous system disorders Neurologic	14.3% 2/14 • Number of events 2 Adverse Events are presented without regard to the specific Adverse Event Term.	13.3% 2/15 • Number of events 2 Adverse Events are presented without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/14 Adverse Events are presented without regard to the specific Adverse Event Term.	26.7% 4/15 • Number of events 4 Adverse Events are presented without regard to the specific Adverse Event Term.
Infections and infestations Infectious disease	7.1% 1/14 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.	6.7% 1/15 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.
Immune system disorders Oncology	7.1% 1/14 • Number of events 1 Adverse Events are presented without regard to the specific Adverse Event Term.	0.00% 0/15 Adverse Events are presented without regard to the specific Adverse Event Term.

Additional Information

Paul Rosenberg, MD

Johns Hopkins University

Phone: 410-550-9883

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place