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

NCT03934138 | Unknown

• 1 other identifier: 2017-A01643-50
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Acute Pain

Keywords

Placebo; Experimental pain

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Anxiety respiratory frequency change

  During the CPT procedure

• Anxiety blood pressure change

  During the CPT procedure

• Knowledge of placebo's mechanisms

  At the beginning and end of the CPT procedures

• 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

  At the end of the study, when all CPT procedures have been carried out, within 10 minutes after the last immersion

Other Outcomes (1)

• Blood pressure

  About 1 minute before every CPT procedures and within 10 secondes after each CPT procedures

Study Arms (2)

Educated open label placebo

ACTIVE COMPARATOR

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

Conventional placebo

PLACEBO COMPARATOR

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

Interventions

Educational movie on placebo mechanisms OTHER

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)

Also known as: Cold Pressure Test (CPT)

Educated open label placebo

Informative movie on hand washing OTHER

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).

Also known as: Cold Pressure Test (CPT)

Conventional placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laboratoire TIMC-IMAG: lead

Study Sites (2)

Leo Druart

Grenoble, France

RECRUITING

Saraeve Graham Longsworth

Grenoble, France

RECRUITING

Related Publications (11)

• 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.

  PMID: 21203519 BACKGROUND

• 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.

  PMID: 28708766 BACKGROUND

• 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.

  PMID: 20592717 BACKGROUND

• 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.

  PMID: 23370213 BACKGROUND

• 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.

  PMID: 29681327 BACKGROUND

• 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.

  PMID: 2277714 BACKGROUND

• 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.

  PMID: 29681324 BACKGROUND

• 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.

  PMID: 15162346 BACKGROUND

• 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.

  PMID: 19540783 BACKGROUND

• 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.

  PMID: 27755279 BACKGROUND

• 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.

  PMID: 31906435 DERIVED

MeSH Terms

Conditions

Acute Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Leo DRUART

  TIMC IMAG Thémas team

  PRINCIPAL INVESTIGATOR

• SaraEve GRAHAM LONGSWORTH

  TIMC IMAG Thémas team

  PRINCIPAL INVESTIGATOR

• Nicolas PINSAULT

  TIMC IMAG Thémas team

  STUDY DIRECTOR

Central Study Contacts

Nicolas PINSAULT

CONTACT

04 76 76 52 56; npinsault@chu-grenoble.fr

Carole ROLLAND

CONTACT

04 76 76 69 03; carole.rolland@univ-grenoble-alpes.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Only the subjects in the the conventional placebo group will be masked. In the educated open label placebo group, subjects will be aware that the cream is inert.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2 groups : Educated open label placebo And Conventional placebo Each of the subjects will undergo the Cold Pressure text procedure under the condition of interest and a control.

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: May 1, 2019
• Study Start: May 3, 2019
• Primary Completion: May 3, 2020
• Study Completion: September 1, 2020
• Last Updated: May 16, 2019

Record last verified: 2019-05

Locations

FR (2)