Conditioned Pharmacotherapeutic Effects in Hypertension

• ClinicalTrials.gov Identifier: NCT02056626
• Recruitment Status: Completed
• First Posted: February 6, 2014
• Results First Posted: June 13, 2019
• Last Update Posted: July 9, 2019
• Sponsor: University of Rochester
• Information provided by (Responsible Party): John Bisognano, University of Rochester

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hypertension	Drug: carvedilol	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Conditioned Pharmacotherapeutic Effects in Hypertension
• Study Start Date: March 2011
• Actual Primary Completion Date: November 30, 2018
• Actual Study Completion Date: December 31, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Mean Systolic Blood Pressure [ Time Frame: day 0 ]
2. Mean Systolic Blood Pressure [ Time Frame: day 14 ]
3. Mean Systolic Blood Pressure [ Time Frame: day 30 ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

University of Rochester

Rochester, New York, United States, 14642

Sponsors and Collaborators

University of Rochester

Investigators

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

  Study Documents (Full-Text)

Documents provided by John Bisognano, University of Rochester:

Study Protocol and Statistical Analysis Plan  [PDF] August 3, 2016

Informed Consent Form  [PDF] March 26, 2015

More Information

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.

LASAGNA L, MOSTELLER F, VON FELSINGER JM, BEECHER HK. A study of the placebo response. Am J Med. 1954 Jun;16(6):770-9.

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.

• Responsible Party: John Bisognano, M.D., Ph.D, University of Rochester
• ClinicalTrials.gov Identifier: NCT02056626
• Other Study ID Numbers: 5R01HL105520 ( U.S. NIH Grant/Contract )
• First Posted: February 6, 2014
• Results First Posted: June 13, 2019
• Last Update Posted: July 9, 2019
• Last Verified: June 2019

Keywords provided by John Bisognano, University of Rochester:

hypertension

Additional relevant MeSH terms:

Hypertension; Vascular Diseases; Cardiovascular Diseases; Carvedilol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antihypertensive Agents; Antioxidants; Protective Agents; Calcium Channel Blockers; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Vasodilator Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists