Conditioned Pharmacotherapeutic Effects in Hypertension

University of Rochester

Status and phase: Completed; Phase 4

Conditions: Hypertension

Treatments: Drug: carvedilol

Study type: Interventional

Funder types: Other

Identifiers

NCT02056626

5R01HL105520

Details and patient eligibility

About

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.

Full description

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:

1. 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:

2. 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

3. 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.

Enrollment: 44 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• systolic blood pressure between 140-160 mmHG
• between 18-80 years old

Exclusion criteria

• abnormal renal function
• currently pregnant, or trying to become pregnant
• being treated with a beta-blocker
• use of illicit drugs

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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44 participants in 4 patient groups

arm 2

Active Comparator group

Description:

partial reinforcement, 6.25 mg twice daily, 25% of time (15 days)

Treatment:

Drug: carvedilol

arm 3

Active Comparator group

Description:

controlled dosing schedule 6.25 mg twice daily (15 days)

Treatment:

Drug: carvedilol

arm 4

Active Comparator group

Description:

controlled dosing schedule 6.25 mg twice daily, every other day (15 days)

Treatment:

Drug: carvedilol

arm 1

Active Comparator group

Description:

standard therapy, 25 mg twice daily (15 days)

Treatment:

Drug: carvedilol