Boosting Open-Label Placebo Effects in Acute Induced Pain in Healthy Adults

NCT ID: NCT05819476

Last Updated: 2025-01-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

141 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-23

Study Completion Date

2025-06-30

Brief Summary

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This study is to investigate the effect of open-label placebo (OLP) application on acute pain in an experimental model of acute pain (simulating wound pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment).

In Part 1 duration of OLP analgesia will be examined, and onset and size of the effect will be reevaluated.

In Part 2 of this study outcomes between subjects receiving one OLP injection, subjects receiving one repetition of the injection on a fixed time point and subjects receiving one repetition of the injection on-demand will be evaluated

Detailed Description

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Pain is highly prevalent in hospital settings. Standard systemic treatment for acute pain consists mainly of basic analgesia. The use of these drugs is often restricted due to their contraindications. Placebo is used nowadays to describe sham treatments and "inert" substances like sugar pills and saline injections. Placebos are proven to elicit clinically significant effects in various conditions, including pain. Ethical concerns about the use of deceptive placebos have prevented their implementation in clinical practice. A possibility to address this issue would be to prescribe placebos openly, that means, without deception. This randomized crossover study evaluates the efficacy of open-label placebo (OLP) in acute pain. Subjective pain ratings and areas of hyperalgesia and allodynia will be measured in a well-established experimental pain model (intradermal electrical stimulation model evoking pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment) and analgesia elicited by OLP injections will be investigated.

In Part 1 duration of OLP analgesia will be examined, and onset and size of the effect will be reevaluated.

In Part 2 of this study outcomes between subjects receiving one OLP injection, subjects receiving one repetition of the injection on a fixed time point and subjects receiving one repetition of the injection on-demand will be evaluated (which leaves the last group a choice over when they would like to have the placebo "booster").

Conditions

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Acute Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

The first part of this study is designed as a confirmatory, randomized, two-arm, assessor-blinded cross-over trial in a monocentric setup at the University Hospital of Basel.

The second part is designed as a proof-of-concept, randomized, controlled, three-arm trial in a monocentric setup at the University Hospital of Basel.
Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Outcome Assessors
In part 1 the assessor won't know whether subjects receive the study intervention or not (single-blinded).

Due to organizational reasons, blinding of the assessor will not be possible in Part 2.

Study Groups

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Part 1: Visit 1 (No treatment) followed by Visit 2 (OLP intervention)

In Part 1, participants will receive one injection (administration of open-label placebo injections without any active ingredient (5 ml 0.9% saline)) at twenty minutes after start of the experiment during the intervention visit 2. Visit 1 (No treatment) will be the control of the study intervention.

Group Type OTHER

OLP-injection

Intervention Type PROCEDURE

Open-label placebo injections without any active ingredient (5 ml 0.9% saline). All participants will be informed that the administered injections are placebo infusions.

Scripted Evidence-based treatment rationale

Intervention Type OTHER

As a second component the intervention will consist of an evidence-based treatment rationale, which will be delivered to patients receiving the intervention prior to the OLP-injections, explaining placebo analgesia in pain in general and specifically in OLP. In the context of OLP treatments this rationale is important in order to create a mental state of positive expectations.

Experimental model of acute pain

Intervention Type OTHER

Experimental model of acute pain (simulating wound pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment).

Part 1: Visit 1 (OLP intervention) followed by Visit 2 (No treatment)

In Part 1, participants will receive one injection (administration of open-label placebo injections without any active ingredient (5 ml 0.9% saline)) at twenty minutes after start of the experiment during the intervention visit 1. Visit 2 (No treatment) will be the control of the study intervention.

Group Type OTHER

OLP-injection

Intervention Type PROCEDURE

Open-label placebo injections without any active ingredient (5 ml 0.9% saline). All participants will be informed that the administered injections are placebo infusions.

Scripted Evidence-based treatment rationale

Intervention Type OTHER

As a second component the intervention will consist of an evidence-based treatment rationale, which will be delivered to patients receiving the intervention prior to the OLP-injections, explaining placebo analgesia in pain in general and specifically in OLP. In the context of OLP treatments this rationale is important in order to create a mental state of positive expectations.

Experimental model of acute pain

Intervention Type OTHER

Experimental model of acute pain (simulating wound pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment).

Part 2/ Group A: 1x OLP (Control)

In Part 2, the Group A (Control) receives just one single OLP injection and no repetition.

Group Type OTHER

OLP-injection

Intervention Type PROCEDURE

Open-label placebo injections without any active ingredient (5 ml 0.9% saline). All participants will be informed that the administered injections are placebo infusions.

Scripted Evidence-based treatment rationale

Intervention Type OTHER

As a second component the intervention will consist of an evidence-based treatment rationale, which will be delivered to patients receiving the intervention prior to the OLP-injections, explaining placebo analgesia in pain in general and specifically in OLP. In the context of OLP treatments this rationale is important in order to create a mental state of positive expectations.

Experimental model of acute pain

Intervention Type OTHER

Experimental model of acute pain (simulating wound pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment).

Part 2/ Group B: 2x OLP; booster time fixed

In Part 2, Group B participants will receive two injections, the first at twenty minutes after start of the experiment, and the second at a time point derived from Part 1 (if data is inconclusive; at 100 minutes).

For every subsequent OLP administration, patients will be reminded of the inertness of the injection and that this injection might help with regulating pain.

Group Type OTHER

OLP-injection

Intervention Type PROCEDURE

Open-label placebo injections without any active ingredient (5 ml 0.9% saline). All participants will be informed that the administered injections are placebo infusions.

Scripted Evidence-based treatment rationale

Intervention Type OTHER

As a second component the intervention will consist of an evidence-based treatment rationale, which will be delivered to patients receiving the intervention prior to the OLP-injections, explaining placebo analgesia in pain in general and specifically in OLP. In the context of OLP treatments this rationale is important in order to create a mental state of positive expectations.

Experimental model of acute pain

Intervention Type OTHER

Experimental model of acute pain (simulating wound pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment).

Part 2/ Group C: 2x OLP; booster on- demand

In Part 2, Group C participants will receive two injections, the first at twenty minutes after start of the experiment, and the second on demand.

For every subsequent OLP administration, patients will be reminded of the inertness of the injection and that this injection might help with regulating pain.

Group Type OTHER

OLP-injection

Intervention Type PROCEDURE

Open-label placebo injections without any active ingredient (5 ml 0.9% saline). All participants will be informed that the administered injections are placebo infusions.

Scripted Evidence-based treatment rationale

Intervention Type OTHER

As a second component the intervention will consist of an evidence-based treatment rationale, which will be delivered to patients receiving the intervention prior to the OLP-injections, explaining placebo analgesia in pain in general and specifically in OLP. In the context of OLP treatments this rationale is important in order to create a mental state of positive expectations.

Experimental model of acute pain

Intervention Type OTHER

Experimental model of acute pain (simulating wound pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment).

Interventions

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OLP-injection

Open-label placebo injections without any active ingredient (5 ml 0.9% saline). All participants will be informed that the administered injections are placebo infusions.

Intervention Type PROCEDURE

Scripted Evidence-based treatment rationale

As a second component the intervention will consist of an evidence-based treatment rationale, which will be delivered to patients receiving the intervention prior to the OLP-injections, explaining placebo analgesia in pain in general and specifically in OLP. In the context of OLP treatments this rationale is important in order to create a mental state of positive expectations.

Intervention Type OTHER

Experimental model of acute pain

Experimental model of acute pain (simulating wound pain: this installation will apply monophasic, rectangular electrical pulses of 0.5ms duration with alternating polarity at 2 Hz frequency. The current will be increased to target a pain rating of 6 of 10 on the NRS (0 = no pain, 10 = worst imaginable pain). Three further adjustments in current will be made every 5 minutes for the next 15 minutes to compensate for habituation. This final current will be kept constant until the end of the particular experiment).

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Healthy volunteers (ASA Class I or II), aged 18 to 65 years
* BMI between 18 and 25kg/m2
* Able to understand the study and the NRS
* Able to give informed consent

Exclusion Criteria

* Participation in a previous open-label placebo study; for Part 2, this includes Part 1 of this study
* Regular intake of medications or drugs potentially interfering with pain sensation (analgesics, opioids, antihistamines, calcium and potassium channel blockers, serotonin/ noradrenaline reuptake inhibitors, corticosteroids)
* Neuropathy
* Chronic pain
* Neuromuscular disease
* Dermatological disease (i.e. Atopic Dermatitis)
* Psychiatric disease
* Pregnancy / Lactation
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tobias Schneider, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesiology, University Hospital of Basel (USB)

Locations

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University Hospital of Basel (USB); Department of Anaesthesiology

Basel, , Switzerland

Site Status RECRUITING

Countries

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Switzerland

Central Contacts

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Tobias Schneider, MD

Role: CONTACT

+41 61 328 65 43

Facility Contacts

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Tobias Schneider, MD

Role: primary

+41 61 328 65 43

References

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de Leeuw M, Laager M, Gaab J, Ruppen W, Schneider T. Boosting open-label placebo effects in acute induced pain in healthy adults (BOLPAP-study): study protocol of a randomized controlled trial. Front Med (Lausanne). 2024 Feb 14;11:1238878. doi: 10.3389/fmed.2024.1238878. eCollection 2024.

Reference Type DERIVED
PMID: 38420356 (View on PubMed)

Other Identifiers

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2023-00296; am23Schneider

Identifier Type: -

Identifier Source: org_study_id

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