Conditioned Pharmacotherapeutic Effects in Hypertension

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: carvedilol

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: arm 2; partial reinforcement, 6.25 mg twice daily, 25% of time (15 days)	Drug: carvedilol
Active Comparator: arm 3; controlled dosing schedule 6.25 mg twice daily (15 days)	Drug: carvedilol
Active Comparator: arm 4; controlled dosing schedule 6.25 mg twice daily, every other day (15 days)	Drug: carvedilol
Active Comparator: arm 1; standard therapy, 25 mg twice daily (15 days)	Drug: carvedilol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Systolic Blood Pressure	day 0
Mean Systolic Blood Pressure	day 14
Mean Systolic Blood Pressure	day 30

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: John D. Bisognano, M.D., Ph.D., University of Rochester

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: February 4, 2014
• First Submitted That Met QC Criteria: February 5, 2014
• First Posted (Estimate): February 6, 2014

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: June 26, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Carvedilol
• Other Study ID Numbers: 5R01HL105520 (U.S. NIH Grant/Contract)