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The proposed research is designed to determine if the application of classical conditioning operations could influence the clinical effects of a regimen of antihypertensive drug therapy. It will be determined if, capitalizing on conditioned pharmacotherapeutic effects, patients can be effectively treated with smaller cumulative amounts of drug.
The proposed research is designed to determine if the application of classical conditioning operations could influence the clinical effects of a regimen of antihypertensive drug therapy. In a double-blind, randomized, parallel-controlled clinical trial, It will be determined if, capitalizing on conditioned pharmacotherapeutic effects, patients can be effectively treated with smaller cumulative amounts of drug. To this end, some hypertensive patients will be treated on a partial rather than a continuous schedule of pharmacologic reinforcement. These patients will be compared to: (a) patients who continue to be treated under a standard regimen of pharmacotherapy at an effective dose of drug, and (b) patients who receive the same (reduced) cumulative amount of medication on a continuous schedule of reinforcement as that received by experimental patients treated under a partial schedule of reinforcement, and (c) patients who receive the same dose and frequency of carvedilol as the Partial Reinforcement Group but receive no intervening conditioned stimuli.
It is possible that a non-continuous schedule of pharmacologic reinforcement (and the concomitant reduced amount of active drug) will exert effects that are indistinguishable from a continuous (standard) regimen of pharmacotherapy (a higher cumulative amount of drug). That outcome or comparison, however, is not critical for evaluating the role of conditioning in the pharmacotherapy of hypertension. Specifically, we will test the hypotheses that:
patients treated under a partial schedule of antihypertensive medication will show a greater amelioration of symptoms than that achieved by patients treated with that same (reduced) amount of drug administered under a continuous schedule of reinforcement;
Conditions permitting, we will also test the predictions that:
irrespective of initial treatment regimen, relapse will occur more quickly following withdrawal of active medication in patients who do not continue to receive conditioned stimuli (placebo) than in patients who continue to receive conditioned stimuli; and
when active drug is withdrawn and replaced by conditioned stimuli alone, resistance to extinction will be greater (i.e., rate of relapse will be less) among patients treated under a partial schedule of reinforcement than patients treated with the same amount of drug administered under a continuous schedule of reinforcement (the partial reinforcement effect).
Positive results would transform the study and practice of pharmacotherapy with respect to placebo effects by providing a new model within which to design treatment protocols for patients with chronic diseases that capitalizes on conditioned pharmacotherapeutic responses. The model, from which testable hypotheses can be derived, also provides a new framework for research on placebo effects and the mechanisms underlying such phenomena.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| arm 2 | Active Comparator | partial reinforcement, 6.25 mg twice daily, 25% of time (15 days) |
|
| arm 3 | Active Comparator | controlled dosing schedule 6.25 mg twice daily (15 days) |
|
| arm 4 | Active Comparator | controlled dosing schedule 6.25 mg twice daily, every other day (15 days) |
|
| arm 1 | Active Comparator | standard therapy, 25 mg twice daily (15 days) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| carvedilol | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Systolic Blood Pressure | day 0 | |
| Mean Systolic Blood Pressure | day 14 | |
| Mean Systolic Blood Pressure | day 30 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John D. Bisognano, M.D., Ph.D. | University of Rochester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Rochester | Rochester | New York | 14642 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15399519 | Background | WOLF S. Effects of suggestion and conditioning on the action of chemical agents in human subjects; the pharmacology of placebos. J Clin Invest. 1950 Jan;29(1):100-9. doi: 10.1172/JCI102225. No abstract available. | |
| 13158365 | Background | LASAGNA L, MOSTELLER F, VON FELSINGER JM, BEECHER HK. A study of the placebo response. Am J Med. 1954 Jun;16(6):770-9. doi: 10.1016/0002-9343(54)90441-6. No abstract available. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Partial Reinforcement | partial reinforcement, 6.25 mg twice daily, 25% of time (15 days) carvedilol |
| FG001 | Controlled Dosing, Daily | controlled dosing schedule 6.25 mg twice daily (15 days) carvedilol |
| FG002 | Controlled Dosing, Every Other Day | controlled dosing schedule 6.25 mg twice daily, every other day (15 days) carvedilol |
| FG003 | Standard Therapy | standard therapy, 25 mg twice daily (15 days) carvedilol |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Partial Reinforcement | partial reinforcement, 6.25 mg twice daily, 25% of time (15 days) carvedilol |
| BG001 | Controlled Dosing, Daily | controlled dosing schedule 6.25 mg twice daily (15 days) carvedilol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Mean Systolic Blood Pressure | Posted | Mean | Standard Deviation | mmHg | day 0 |
|
30 days
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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 | Partial Reinforcement | partial reinforcement, 6.25 mg twice daily, 25% of time (15 days) carvedilol |
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This study was under enrolled and therefore not powered to answer the hypothesis.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Bisognano | University of Rochester | 585-341-7800 | john_bisognano @ urmc.rochester.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 3, 2016 | May 21, 2019 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 26, 2015 | May 23, 2019 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular 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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| 14153340 | Background | KNOWLES JB. CONDITIONING AND THE PLACEBO EFFECT: THE EFFECTS OF DECAFFEINATED COFFEE ON SIMPLE REACTION TIME IN HABITUAL COFFEE DRINKERS. Behav Res Ther. 1963 Aug;1:151-7. doi: 10.1016/0005-7967(63)90018-4. No abstract available. |
| BG002 | Controlled Dosing, Every Other Day | controlled dosing schedule 6.25 mg twice daily, every other day (15 days) carvedilol |
| BG003 | Standard Therapy | standard therapy, 25 mg twice daily (15 days) carvedilol |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Number of participants taking other antihypertensives | Count of Participants | Participants |
|
| Mean systolic blood pressure | Mean | Standard Deviation | mmHg |
|
| OG003 |
| Standard Therapy |
standard therapy, 25 mg twice daily (15 days) carvedilol |
|
|
| Primary | Mean Systolic Blood Pressure | Posted | Mean | Standard Deviation | mmHg | day 14 |
|
|
|
| Primary | Mean Systolic Blood Pressure | Posted | Mean | Standard Deviation | mmHg | day 30 |
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Controlled Dosing, Daily | controlled dosing schedule 6.25 mg twice daily (15 days) carvedilol | 0 | 13 | 0 | 13 | 0 | 13 |
| EG002 | Controlled Dosing, Every Other Day | controlled dosing schedule 6.25 mg twice daily, every other day (15 days) carvedilol | 0 | 4 | 0 | 4 | 0 | 4 |
| EG003 | Standard Therapy | standard therapy, 25 mg twice daily (15 days) carvedilol | 0 | 14 | 0 | 14 | 0 | 14 |
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| 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 |