Trial of Carvedilol in Alzheimer's Disease

NCT ID: NCT01354444

Last Updated: 2018-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2017-01-31

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.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Carvedilol

Intervention Type: DRUG

target dose of 25 mg daily which is half the maximum dose used in clinical practice

Placebo

Non active substance

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

a pill that will look like the active drug but will not contain any carvedilol

Interventions

Carvedilol

target dose of 25 mg daily which is half the maximum dose used in clinical practice

Intervention Type: DRUG

Placebo

a pill that will look like the active drug but will not contain any carvedilol

Intervention Type: DRUG

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.

• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul B. Rosenberg, M.D.

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins School of Medicine Bayview Campus

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

NA_00035546

Identifier Type: -

Identifier Source: org_study_id