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Trial of Carvedilol in Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Carvedilol
Placebo
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Memory problems, Alzheimer's Disease

Eligibility Criteria

undefined - 100 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of AD by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria
  • Mini-Mental State Exam (MMSE) 16-26. This range corresponds roughly to "mild" AD as rated by CDR below, and provides a rapid test for efficient screening of potential participants.
  • Clinical Dementia Rating (CDR) < 1 (mild dementia). This corresponds with "early" AD. Participants will be eligible if they have AD diagnosis and CDR of 0.5 or 1.0. The category of CDR 0.5 AD is particularly important to include as these participants are in the earliest stage that can be diagnosed as dementia (as opposed to mild cognitive impairment) and thus are in the "earliest" clinical stage of AD.
  • Patients will be allowed to remain on current FDA-approved Alzheimer's treatments including cholinesterase inhibitors and memantine, so long as the dose has been stable for >= 3 months. These medications lack any notable effects on amyloid synthesis or metabolism and thus there is no reason to exclude them. The rationale behind requiring a stable dose is so that change in the trial can be attributed to the study intervention rather than recent changes of other medications affecting cognition.
  • Patients will be allowed to remain on antidepressant and antipsychotics medications so long as the dose has been stable for >= 3 months. The rationale is the same as above.
  • Knowledgeable informant available for all study visits. This is standard practice in AD research because many standard instruments and questionnaires in this trial require a knowledgeable informant.

Exclusion criteria

  • Evidence of non-AD dementias including Huntington's disease, Parkinson's disease, or frontotemporal dementia.

    2.Current Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-IV Axis I diagnoses other than dementia, including major depression, bipolar disorder, schizophrenia, anxiety disorders, alcohol abuse, or other substance abuse. These diagnoses would merit their own treatment plans and changes in these conditions could significantly affect cognitive and functional outcomes, confounding our efforts to study the efficacy of the study intervention.

  • Any clinically significant medical condition that could interfere with the subject's ability to safely participate in the study or to be followed.
  • Current use of Beta-blocking agents.
  • Contraindications to use of Beta-blocking agents, to be determined in consultation with the patient's primary care physician or (if appropriate) cardiologist.
  • Clinically significant hepatic or renal insufficiency.

Sites / Locations

  • Johns Hopkins School of Medicine Bayview Campus

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Carvedilol

Placebo

Arm Description

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.

Non active substance

Outcomes

Primary Outcome Measures

Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months
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.

Secondary Outcome Measures

Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers
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.
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers
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).

Full Information

First Posted
May 9, 2011
Last Updated
January 8, 2018
Sponsor
Johns Hopkins University
Collaborators
Icahn School of Medicine at Mount Sinai
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1. Study Identification

Unique Protocol Identification Number
NCT01354444
Brief Title
Trial of Carvedilol in Alzheimer's Disease
Official Title
Pilot Trial of Carvedilol in Alzheimer's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
June 2011 (Actual)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
Icahn School of Medicine at Mount Sinai

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a 6-month pilot randomized double-blind placebo-controlled trial of carvedilol, with the primary objective being to determine whether carvedilol treatment is associated with improvement in Alzheimer's Disease (AD) as compared to placebo treatment. Secondary objectives are to monitor changes in cerebrospinal fluid amyloid levels and whether this dose will be safe and well-tolerated in AD patients. Clinical assessments will be performed at baseline, 3 months, and 6 months, while cerebrospinal fluid and blood samples will be obtained at baseline and 6 months.
Detailed Description
The purpose of the study is to measure decline in episodic memory in participants with early AD taking carvedilol compared to placebo treatment as evidenced by the Hopkins Verbal Learning Test (HVLT). cerebrospinal fluid levels of Aβ oligomers in early AD, will be measured in participants receiving carvedilol treatment when compared to placebo treatment. Adverse effects will be monitored in participants receiving carvedilol when compared to placebo. To assess adverse events, routine chemistry and hematology studies, vital signs, and electrocardiographic parameters before and after 6 months randomized placebo-controlled double-blind treatment with carvedilol at a target dose of 25 mg daily, comparing 25 early AD participants taking carvedilol vs. 25 early AD participants taking placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Memory problems, Alzheimer's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Non active substance
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Description
target dose of 25 mg daily which is half the maximum dose used in clinical practice
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
a pill that will look like the active drug but will not contain any carvedilol
Primary Outcome Measure Information:
Title
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months
Description
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.
Time Frame
Baseline, 3 months, and 6 months
Secondary Outcome Measure Information:
Title
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers
Description
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.
Time Frame
6 months
Title
Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers
Description
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).
Time Frame
6 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of AD by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria Mini-Mental State Exam (MMSE) 16-26. This range corresponds roughly to "mild" AD as rated by CDR below, and provides a rapid test for efficient screening of potential participants. Clinical Dementia Rating (CDR) < 1 (mild dementia). This corresponds with "early" AD. Participants will be eligible if they have AD diagnosis and CDR of 0.5 or 1.0. The category of CDR 0.5 AD is particularly important to include as these participants are in the earliest stage that can be diagnosed as dementia (as opposed to mild cognitive impairment) and thus are in the "earliest" clinical stage of AD. Patients will be allowed to remain on current FDA-approved Alzheimer's treatments including cholinesterase inhibitors and memantine, so long as the dose has been stable for >= 3 months. These medications lack any notable effects on amyloid synthesis or metabolism and thus there is no reason to exclude them. The rationale behind requiring a stable dose is so that change in the trial can be attributed to the study intervention rather than recent changes of other medications affecting cognition. Patients will be allowed to remain on antidepressant and antipsychotics medications so long as the dose has been stable for >= 3 months. The rationale is the same as above. Knowledgeable informant available for all study visits. This is standard practice in AD research because many standard instruments and questionnaires in this trial require a knowledgeable informant. Exclusion criteria Evidence of non-AD dementias including Huntington's disease, Parkinson's disease, or frontotemporal dementia. 2.Current Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-IV Axis I diagnoses other than dementia, including major depression, bipolar disorder, schizophrenia, anxiety disorders, alcohol abuse, or other substance abuse. These diagnoses would merit their own treatment plans and changes in these conditions could significantly affect cognitive and functional outcomes, confounding our efforts to study the efficacy of the study intervention. Any clinically significant medical condition that could interfere with the subject's ability to safely participate in the study or to be followed. Current use of Beta-blocking agents. Contraindications to use of Beta-blocking agents, to be determined in consultation with the patient's primary care physician or (if appropriate) cardiologist. Clinically significant hepatic or renal insufficiency.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul B. Rosenberg, M.D.
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins School of Medicine Bayview Campus
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States

12. IPD Sharing Statement

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Trial of Carvedilol in Alzheimer's Disease

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