Trial of Carvedilol in Alzheimer's Disease

NCT01354444 | Completed Phase 4 Results DMC

• 1 other identifier: NA_00035546
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Keywords

Memory problems; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 3 months, and 6 months

Secondary Outcomes (2)

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

  6 months

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

  6 months

Study Arms (2)

Carvedilol

ACTIVE COMPARATOR

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.

Drug: Carvedilol

Placebo

PLACEBO COMPARATOR

Non active substance

Drug: Placebo

Interventions

Carvedilol DRUG

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

Carvedilol

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: Up to 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

Johns Hopkins School of Medicine Bayview Campus

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Memory Disorders

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Paul Rosenberg, MD
• Organization: Johns Hopkins University

prosenb9@jhmi.edu

410-550-9883

Study Officials

• Paul B. Rosenberg, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2011
• First Posted: May 16, 2011
• Study Start: June 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: January 1, 2017
• Last Updated: February 6, 2018
• Results First Posted: February 6, 2018

Record last verified: 2018-01

Locations

US (1)