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

NCT05819476 | Recruiting

• 1 other identifier: 2023-00296; am23Schneider
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Pain

Keywords

Open-Label Placebo (OLP); OLP analgesia; acute pain; hyperalgesia; allodynia

Outcome Measures

Primary Outcomes (2)

• Part 1: Change in Area under the Pain Curve (AUPC)

  Area under the Pain Curve (AUPC) using the numeric rating scale (NRS; 0 = no pain, 10 = worst imaginable pain) during three hours after administering an OLP

  During three hours after administering an OLP

• Part 2: Change in Area under the Pain Curve (AUPC)

  Area under the Pain Curve (AUPC) using the numeric rating scale (NRS; 0 = no pain, 10 = worst imaginable pain). Comparison of the AUPCs of subjects receiving just one OLP injection with subjects additionally receiving one repetition of OLP administration at a time point derived from Part 1 and subjects getting the second OLP injection on-demand.

  During three hours after administering an OLP

Secondary Outcomes (3)

• Part 1 and 2: Change in subjective pain ratings on each measurement point using the numeric rating scale (NRS)

  Up to 200 minutes after electrical pain stimulation

• Part 1 and 2: Change in Area under the Curve (AUC) of area of hyperalgesia

  Up to 200 minutes after electrical pain stimulation

• Part 1 and 2: Change in Area under the Curve (AUC) of area of allodynia

  Up to 200 minutes after electrical pain stimulation

Study Arms (5)

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

OTHER

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.

Procedure: OLP-injection; Other: Scripted Evidence-based treatment rationale; Other: Experimental model of acute pain

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

OTHER

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.

Procedure: OLP-injection; Other: Scripted Evidence-based treatment rationale; Other: Experimental model of acute pain

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

OTHER

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

Procedure: OLP-injection; Other: Scripted Evidence-based treatment rationale; Other: Experimental model of acute pain

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

OTHER

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.

Procedure: OLP-injection; Other: Scripted Evidence-based treatment rationale; Other: Experimental model of acute pain

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

OTHER

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.

Procedure: OLP-injection; Other: Scripted Evidence-based treatment rationale; Other: Experimental model of acute pain

Interventions

OLP-injection 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.

Part 1: Visit 1 (No treatment) followed by Visit 2 (OLP intervention); Part 1: Visit 1 (OLP intervention) followed by Visit 2 (No treatment); Part 2/ Group A: 1x OLP (Control); Part 2/ Group B: 2x OLP; booster time fixed; Part 2/ Group C: 2x OLP; booster on- demand

Scripted Evidence-based treatment rationale 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.

Part 1: Visit 1 (No treatment) followed by Visit 2 (OLP intervention); Part 1: Visit 1 (OLP intervention) followed by Visit 2 (No treatment); Part 2/ Group A: 1x OLP (Control); Part 2/ Group B: 2x OLP; booster time fixed; Part 2/ Group C: 2x OLP; booster on- demand

Experimental model of acute pain 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 (No treatment) followed by Visit 2 (OLP intervention); Part 1: Visit 1 (OLP intervention) followed by Visit 2 (No treatment); Part 2/ Group A: 1x OLP (Control); Part 2/ Group B: 2x OLP; booster time fixed; Part 2/ Group C: 2x OLP; booster on- demand

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital of Basel (USB); Department of Anaesthesiology

Basel, 4031, Switzerland

RECRUITING

Related Publications (1)

• 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.

  PMID: 38420356 DERIVED

MeSH Terms

Conditions

Acute Pain; Hyperalgesia

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatosensory Disorders; Sensation Disorders; Nervous System Diseases

Study Officials

• Tobias Schneider, MD

  Department of Anaesthesiology, University Hospital of Basel (USB)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobias Schneider, MD

CONTACT

+41 61 328 65 43; tobias.schneider@usb.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 20, 2023
• First Posted: April 19, 2023
• Study Start: March 23, 2023
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 24, 2025

Record last verified: 2025-01

Locations

CH (1)