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Trial of Carvedilol in Alzheimer's Disease

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.
 
ClinicalTrials.gov Identifier: NCT01354444
Recruitment Status : Completed
First Posted : May 16, 2011
Results First Posted : February 6, 2018
Last Update Posted : February 6, 2018
Sponsor:
Collaborator:
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE May 9, 2011
First Posted Date  ICMJE May 16, 2011
Results First Submitted Date  ICMJE October 26, 2017
Results First Posted Date  ICMJE February 6, 2018
Last Update Posted Date February 6, 2018
Actual Study Start Date  ICMJE June 2011
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
Hopkins Verbal Learning Test (HVLT) Scores at Baseline, 3, and 6 Months [ Time Frame: Baseline, 3 months, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2011)
To determine whether carvedilol treatment has a beneficial effect on episodic recall [ Time Frame: 6 months ]
We 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Effect of Carvedilol Treatment 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 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 [ 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 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2011)
To determine whether carvedilol treatment is associated with decrease in CSF levels of amyloid-beta oligomers [ Time Frame: 6 months ]
We 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial of Carvedilol in Alzheimer's Disease
Official Title  ICMJE Pilot Trial of Carvedilol in Alzheimer's Disease
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: Carvedilol
    target dose of 25 mg daily which is half the maximum dose used in clinical practice
  • Drug: Placebo
    a pill that will look like the active drug but will not contain any carvedilol
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Carvedilol
  • Placebo Comparator: Placebo
    Non active substance
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 8, 2018)
29
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2011)
50
Actual Study Completion Date  ICMJE January 2017
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 100 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01354444
Other Study ID Numbers  ICMJE NA_00035546
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Johns Hopkins University
Original Responsible Party Paul Rosenberg, M.D., Johns Hopkins University School of Medicine
Current Study Sponsor  ICMJE Johns Hopkins University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Icahn School of Medicine at Mount Sinai
Investigators  ICMJE
Principal Investigator: Paul B. Rosenberg, M.D. Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP