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Trial of Carvedilol in Alzheimer's Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01354444
First Posted: May 16, 2011
Last Update Posted: October 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Johns Hopkins University
  Purpose
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.

Condition Intervention Phase
Alzheimer's Disease Drug: Carvedilol Drug: Placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Pilot Trial of Carvedilol in Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • To determine whether carvedilol treatment has a beneficial effect on episodic recall [ Time Frame: 6 months ]
    The investigators will measure 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, comparing changes in HVLT Immediate and Delayed Recall score in 25 AD participants taking carvedilol vs. 25 AD participants taking placebo.


Secondary Outcome Measures:
  • To determine whether carvedilol treatment is associated with decrease in cerebrospinal fluid (CSF) levels of amyloid-beta oligomers [ Time Frame: 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 25 AD participants taking carvedilol vs. 25 AD participants taking placebo.


Enrollment: 30
Actual Study Start Date: June 2011
Study Completion Date: January 2017
Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: Carvedilol
target dose of 25 mg daily which is half the maximum dose used in clinical practice
Placebo Comparator: Placebo
Non active substance
Drug: Placebo
a pill that will look like the active drug but will not contain any carvedilol

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 100 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01354444


Locations
United States, Maryland
Johns Hopkins School of Medicine Bayview Campus
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Icahn School of Medicine at Mount Sinai
Investigators
Principal Investigator: Paul B. Rosenberg, M.D. Johns Hopkins University
  More Information

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01354444     History of Changes
Other Study ID Numbers: NA_00035546
First Submitted: May 9, 2011
First Posted: May 16, 2011
Last Update Posted: October 11, 2017
Last Verified: October 2017

Keywords provided by Johns Hopkins University:
Memory problems
Alzheimer's Disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Carvedilol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists