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Trial of Carvedilol in Alzheimer's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Johns Hopkins University
Sponsor:
Collaborator:
Mount Sinai School of Medicine
Information provided by (Responsible Party):
Paul B. Rosenberg, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01354444
First received: May 9, 2011
Last updated: September 17, 2013
Last verified: September 2013

May 9, 2011
September 17, 2013
June 2011
June 2014   (final data collection date for primary outcome measure)
To determine whether carvedilol treatment has a beneficial effect on episodic recall [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
To determine whether carvedilol treatment has a beneficial effect on episodic recall [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
Complete list of historical versions of study NCT01354444 on ClinicalTrials.gov Archive Site
To determine whether carvedilol treatment is associated with decrease in CSF levels of amyloid-beta oligomers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
To determine whether carvedilol treatment is associated with decrease in CSF levels of amyloid-beta oligomers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
Not Provided
Not Provided
 
Trial of Carvedilol in Alzheimer's Disease
Pilot Trial of Carvedilol in Alzheimer's Disease

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.

The purpose of the study is measure decline in episodic memory, in participants taking carvedilol in early AD, when 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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Alzheimer's Disease
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
June 2015
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Diagnosis of AD by NINCDS/ADRDA criteria (47)
  2. 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.
  3. Clinical Dementia Rating (CDR) < 1 (mild dementia). This corresponds with "early" AD (see D.2.5 above). 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.
  4. 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.
  5. 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 item 5.
  6. Knowledgeable informant available for all study visits. This is standard practice in AD research because many standard instruments (in this trial including CDR, NPI, ADCS-ADL) require a knowledgeable informant.

Exclusion criteria

  1. Evidence of non-AD dementias including Huntington's disease, Parkinson's disease, or frontotemporal dementia.
  2. Current 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.
  3. Any clinically significant medical condition that could interfere with the subject's ability to safely participate in the study or to be followed.
  4. Current use of Beta-blocking agents
  5. Contraindications to use of Beta-blocking agents, to be determined in consultation with the patient's primary care physician or (if appropriate) cardiologist.
  6. Clinically significant hepatic or renal insufficiency.
Both
Not Provided
No
Contact: Paul B Rosenberg, MD 410-550-9883 prosenb9@jhmi.edu
Contact: Julia J. Pedroso, RN, MA 410-550-9054 jpedroso@jhmi.edu
United States
 
NCT01354444
1 R01 AG037504-01
Yes
Paul B. Rosenberg, Johns Hopkins University
Johns Hopkins University
Mount Sinai School of Medicine
Principal Investigator: Paul B. Rosenberg, M.D. Johns Hopkins University
Johns Hopkins University
September 2013

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