Does the Understanding of Placebo Mechanisms Compensate for the Loss of Efficacy Associated With Open Label Placebo (PLACETHIC)

Does the Subject's Understanding of Underlying Placebo Mechanisms Compensate for the Loss of Efficacy Associated With the Disclosure of the Use of a Placebo

The investigators are investigating whether, when given detailed information about underlying placebo mechanisms and pain, subjects will have a response similar to that of those subjected to a procedure in which they receive a conventional placebo treatment (associated with deception).

STUDY DESIGN: This is a non-inferior parallel, controlled and randomized, single blind trial.

POPULATION: The investigators will include in the study 126 subjects without known pathology. Participants will then be divided into 2 groups on a randomized basis.

METHODOLOGY: Each subject will undergo three sessions of Cold Pressure Test (CPT), a cold pain stimulation method: calibration, condition of interest (conventional placebo or educated placebo) and control. The investigators' main judgment criterion is be the difference in pain intensity experienced on the visual analog scale between the CPT control and the CPT under the condition of interest.

This study will allow the investigators to rule on the non-inferiority of an educated open label placebo compared to a conventional placebo in the context of an acute painful stimulation.

Study Overview

• Status: Unknown
• Conditions: Acute Pain
• Intervention / Treatment: Other: Educational movie on placebo mechanisms; Other: Informative movie on hand washing

• Study Type: Interventional
• Enrollment (Anticipated): 126
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Grenoble, France
    • Recruiting
    • Leo Druart
  • Grenoble, France
    • Recruiting
    • Saraeve Graham Longsworth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Person affiliated to Social Security
• Informed consent, written and signed by the subject.

Exclusion Criteria:

• Persons referred to in Articles L1121-5 to L1121-8 of the Public Health Code (CSP), which corresponds to all protected persons: pregnant women, parturient women, nursing mothers, persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure, cannot be included in clinical trials.
• Persons with a pathology against indicating the use of CPT experimentally induced pain :
• Any pathologies affecting the venous, arterial or lymphatic system
• Diabetes
• Cardiac disorders
• Asthma
• Frostbite
• Epilepsy
• Arthritis
• Lupus erythematosus
• Allergy to Cremafluid® cream
• Person with concomitant treatment that modifies sensitivity to pain, chronic or acute at the time of the experiment, such as analgesics, psychotropic drugs or anti-inflammatories.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Educated open label placebo; These subjects will undergo all the same procedures as in the control group. But before the placebo CTP, they will watch a short movie explaining placebo mechanisms. While applying the placebo cream, they will be told that the cream is inert (placebo), efficient to decrease pain caused by cold and the mechanisms seen in the movie will take place.	Other: Educational movie on placebo mechanisms; Educational movie on placebo mechanisms : animated video, duration : 12 minutes. It will be followed by the CPTs : experimentally induced pain by keeping the non dominant hand in cold water (1° Celsius) for a limited time. The duration of immersion is personal and calibrated to be around to ensure that the intensity of pain will be homogeneous (around 7/10 on the visual analogue scale with no treatment); Other Names: Cold Pressure Test (CPT)
PLACEBO_COMPARATOR: Conventional placebo; These subjects will watch a video on hand washing. While applying the placebo cream, they will be told that this cream is effective to decreased pain caused by cold.	Other: Informative movie on hand washing; Animated video, duration : 11 minutes. It will be followed by the CPTs : experimentally induced pain by keeping the non dominant hand in cold water (1° Celsius) for a limited time. The duration of immersion is personal and calibrated to be around to ensure that the intensity of pain will be homogeneous (around 7/10 on the visual analogue scale with no treatment).; Other Names: Cold Pressure Test (CPT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity: Visual Analogue Scale (VAS)	Evaluated with a Visual Analogue Scale (VAS) from 0 to 100 mm, with a non inferiority margin at 10 mm and a standard deviation at 22 mm.	At the end of the CPT procedure, within 30 seconds after the removal of the hand from the CPT cold water tank.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety respiratory frequency change	Evaluated thanks to the respiratory frequency collect with a PneumoTrace belt through LabChart software.	During the CPT procedure
Anxiety blood pressure change	Evaluated thanks to the automatic blood pressure monitor (both systolic/diastolic blood pressure, heart rate)	During the CPT procedure
Knowledge of placebo's mechanisms	Evaluated with a questionnaire made for this study with 17 questions about placebo mechanisms.	At the beginning and end of the CPT procedures
Perception of the investigator	The perception of the investigator will be evaluated by a visual analogue scale "perception of the investigator".	At the end of the study, when all CPT procedures have been carried out, within 10 minutes after the last immersion
The Perceived Awareness of the Research Hypothesis Scale questionnaire	Perception of the research hypothesis with the Rubin Questionnaire. Perceived Awareness of the Research Hypothesis " (PARH) wich is a scale of 4-item quantitative self-report method for measuring the potential influence of demand characteristics in research situations	At the end of the study, when all CPT procedures have been carried out, within 10 minutes after the last immersion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Safety measure to insure blood pressure does not exceed 150/90mmHg (both systolic/diastolic blood pressure, heart rate)	About 1 minute before every CPT procedures and within 10 secondes after each CPT procedures

Collaborators and Investigators

• Sponsor: Laboratoire TIMC-IMAG
• Investigators: Principal Investigator: Leo DRUART, TIMC IMAG Thémas team; Principal Investigator: SaraEve GRAHAM LONGSWORTH, TIMC IMAG Thémas team; Study Director: Nicolas PINSAULT, TIMC IMAG Thémas team

Publications and helpful links

General Publications

• Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP, Kowalczykowski M, Miller FG, Kirsch I, Lembo AJ. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One. 2010 Dec 22;5(12):e15591. doi: 10.1371/journal.pone.0015591.
• Locher C, Frey Nascimento A, Kirsch I, Kossowsky J, Meyer A, Gaab J. Is the rationale more important than deception? A randomized controlled trial of open-label placebo analgesia. Pain. 2017 Dec;158(12):2320-2328. doi: 10.1097/j.pain.0000000000001012.
• Benedetti F, Carlino E, Pollo A. How placebos change the patient's brain. Neuropsychopharmacology. 2011 Jan;36(1):339-54. doi: 10.1038/npp.2010.81. Epub 2010 Jun 30.
• Benedetti F, Amanzio M. Mechanisms of the placebo response. Pulm Pharmacol Ther. 2013 Oct;26(5):520-3. doi: 10.1016/j.pupt.2013.01.006. Epub 2013 Jan 28.
• Colloca L, Howick J. Placebos Without Deception: Outcomes, Mechanisms, and Ethics. Int Rev Neurobiol. 2018;138:219-240. doi: 10.1016/bs.irn.2018.01.005. Epub 2018 Apr 4.
• Voudouris NJ, Peck CL, Coleman G. The role of conditioning and verbal expectancy in the placebo response. Pain. 1990 Oct;43(1):121-128. doi: 10.1016/0304-3959(90)90057-K.
• Pecina M, Zubieta JK. Expectancy Modulation of Opioid Neurotransmission. Int Rev Neurobiol. 2018;138:17-37. doi: 10.1016/bs.irn.2018.02.003. Epub 2018 Apr 2.
• Mitchell LA, MacDonald RA, Brodie EE. Temperature and the cold pressor test. J Pain. 2004 May;5(4):233-7. doi: 10.1016/j.jpain.2004.03.004.
• Streff A, Kuehl LK, Michaux G, Anton F. Differential physiological effects during tonic painful hand immersion tests using hot and ice water. Eur J Pain. 2010 Mar;14(3):266-72. doi: 10.1016/j.ejpain.2009.05.011. Epub 2009 Jun 21.
• Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain. 2016 Dec;157(12):2766-2772. doi: 10.1097/j.pain.0000000000000700. Erratum In: Pain. 2017 Feb;158(2):365.
• Druart L, Graham Longsworth S, Rolland C, Dolgopoloff M, Terrisse H, Bosson JL, Pinsault N. Can an Open-Label Placebo Be as Effective as a Deceptive Placebo? Methodological Considerations of a Study Protocol. Medicines (Basel). 2020 Jan 2;7(1):3. doi: 10.3390/medicines7010003.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 3, 2019
• Primary Completion (ANTICIPATED): May 3, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (ACTUAL): May 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 16, 2019
• Last Update Submitted That Met QC Criteria: May 14, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Placebo; Experimental pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: 2017-A01643-50

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No