Trial of Carvedilol in Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Carvedilol; Placebo
Intervention description: target dose of 25 mg daily which is half the maximum dose used in clinical practice; a pill that will look like the active drug but will not contain any carvedilol
Intervention MeSH terms: Carvedilol
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 29.0
Sex: All
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Memory problems; Alzheimer's Disease

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.
    

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.