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

Acute Pain Clinical Trial

— PLACETHIC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03934138
• Other study ID #: 2017-A01643-50
• Status: Recruiting
• Phase: N/A
• Start date: May 3, 2019
• Est. completion date: September 1, 2020

Study information

• Verified date: May 2019
• Source: Laboratoire TIMC-IMAG
• Contact: Nicolas PINSAULT
• Phone: 04 76 76 52 56
• Email: npinsault[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: September 1, 2020
• Est. primary completion date: May 3, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Pain

Intervention

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)
• 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).

Locations

Country	Name	City	State
France	Leo Druart	Grenoble
France	Saraeve Graham Longsworth	Grenoble

Sponsors (1)

Lead Sponsor	Collaborator
Laboratoire TIMC-IMAG

Country where clinical trial is conducted

France, 

References & Publications (10)

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. Review. — View Citation

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. Review. — View Citation

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. Erratum in: Pain. 2017 Feb;158(2):365. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Mitchell LA, MacDonald RA, Brodie EE. Temperature and the cold pressor test. J Pain. 2004 May;5(4):233-7. — View Citation

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. Review. — View Citation

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. — View Citation

Voudouris NJ, Peck CL, Coleman G. The role of conditioning and verbal expectancy in the placebo response. Pain. 1990 Oct;43(1):121-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	Anxiety respiratory frequency change	Evaluated thanks to the respiratory frequency collect with a PneumoTrace belt through LabChart software.	During the CPT procedure
Secondary	Anxiety blood pressure change	Evaluated thanks to the automatic blood pressure monitor (both systolic/diastolic blood pressure, heart rate)	During the CPT procedure
Secondary	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
Secondary	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
Secondary	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