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| Name | Class |
|---|---|
| Icahn School of Medicine at Mount Sinai | OTHER |
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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 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Placebo | Placebo Comparator | Non active substance |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carvedilol | Drug | target dose of 25 mg daily which is half the maximum dose used in clinical practice |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers | 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. |
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Inclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Paul B. Rosenberg, M.D. | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins School of Medicine Bayview Campus | Baltimore | Maryland | 21224 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Carvedilol: target dose of 25 mg daily which is half the maximum dose used in clinical practice |
| FG001 | Placebo | Non active substance Placebo: a pill that will look like the active drug but will not contain any carvedilol |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Carvedilol: target dose of 25 mg daily which is half the maximum dose used in clinical practice |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | Scores on a scale | Baseline, 3 months, and 6 months |
|
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Adverse Events are presented without regard to the specific Adverse Event Term.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Carvedilol: target dose of 25 mg daily which is half the maximum dose used in clinical practice |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HEME | Blood and lymphatic system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HEME | Blood and lymphatic system disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul Rosenberg, MD | Johns Hopkins University | 410-550-9883 | prosenb9@jhmi.edu |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D008569 | Memory Disorders |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077261 | Carvedilol |
| ID | Term |
|---|---|
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Placebo | Drug | a pill that will look like the active drug but will not contain any carvedilol |
|
| 6 months |
| Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers | 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). | 6 months |
Non active substance Placebo: a pill that will look like the active drug but will not contain any carvedilol |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| HVLT Score in Treatment Group |
Descriptive statistics for immediate recall in the Hopkins Verbal Learning Test in the treatment group |
|
|
|
| Secondary | Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers | 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. | Posted | Mean | Standard Deviation | pg/mL | 6 months |
|
|
|
|
| Secondary | Effect of Carvedilol Treatment in Cerebrospinal Fluid (CSF) Levels of Amyloid-beta Oligomers | 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). | Posted | Mean | Standard Deviation | ng/mL | 6 months |
|
|
|
| 2 |
| 14 |
| 12 |
| 14 |
| EG001 | Placebo | Non active substance Placebo: a pill that will look like the active drug but will not contain any carvedilol | 1 | 15 | 12 | 15 |
| GI | Gastrointestinal disorders |
|
| Neurologic | Nervous system disorders |
|
| Cardiac | Cardiac disorders |
|
| Systemic | Nervous system disorders |
|
| Dermatologic | Skin and subcutaneous tissue disorders |
|
| Psychiatric | Psychiatric disorders |
|
| GI | Gastrointestinal disorders |
|
| Neurologic | Nervous system disorders |
|
| Arthritis | Musculoskeletal and connective tissue disorders |
|
| Infectious disease | Infections and infestations |
|
| Oncology | Immune system disorders |
|
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020005 |
| Propanols |
| D000588 | Amines |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
| Baseline P tau (pg/mL) |
|
| Six month Tau (pg/mL) |
|
| Six month ABeta42 (pg/mL) |
|
| Six month P tau (pg/mL) |
|
| Rank sum test |
| 0.0562 |
| Other |
| This analysis compares the change in p-tau between the treatment and placebo group from baseline to 6 months later. | Rank sum test | 0.314 | Other |
| This analysis compares the change in oligomeric Abeta between the treatment and placebo group from baseline to 6 months later. | Rank sum test | 0.438 | Other |