Can Training Increase Reporting Accuracy and Study Power in Human Pain Trials

Not Applicable

• Conditions: Healthy; Placebo Response
• Interventions: Drug: Ibuprofen 400 mg; Drug: Placebo oral tablet

• Registration Number: NCT03952715
• Lead Sponsor: University of Haifa

Brief Summary

In previous studies, results of both the Focused Analgesia Selection Test (FAST) procedure, a method to assess pain-reporting accuracy, and the Evoked Pain Training (EPT) procedure, aimed to improve pain-reporting accuracy, correlated with the placebo response. The objectives of the current project were to determine if EPT (1) increases pain reporting accuracy and (2) affect the placebo response in experimental pain study.

Detailed Description

Analgesic trials suffer from low assay-sensitivity, and experts in the field are concerned that many previous negative analgesic trails might be regarded as failed trails. Major contributor to this concern is the large placebo response observed in analgesic clinical trials. Recent findings from the investigators group suggest that improving pain reporting accuracy could increase analgesic trials assay sensitivity by reducing the placebo response. In previous studies, the investigators developed the Focused Analgesia Selection Test (FAST), a method to assess pain reporting accuracy. Later on, the investigators developed the Evoked Pain Training (EPT), aimed to improve pain reporting accuracy. Both these methods constitute the core of this project. The objectives of the current project are to determine if subject training increases (1) pain reporting accuracy and (2) the power of an analgesic trial.

Summary of main methods This project objectives will be achieved by preforming a two-stage study. First, all subjects undergo baseline assessments, including assessment of pain reporting accuracy (the FAST procedure) (visit #1). Then, subjects enter the first study stage (training stage), in which half of study subjects (n=50) undergo training to improve pain reporting accuracy. The training comprise of three in-clinic visits (visits #2, 3, 4) in which subjects receive feedback on accuracy of pain reports in response to noxious stimuli of various intensities (the EPT procedure). The EPT is based on repeated application of the FAST procedure, while providing feedback to subjects in between applications. The other half of subjects (n=50) undergo a "shame-training". After completion of the training phase, all subjects enter an experimental cross-over study design (second study phase) comprised of two in-clinic visits (visits 5 and 6). In each of these two visits, subjects undergo a battery of experimental pain tests (pre-treatment assessment), take one of two pills (either Ibuprofen 400 mg or identical sugar pill) in a random order, wait approximately 1 hour, and then undergo the same pain tests again (post-treatment assessment).

Study Timeline

• Study Start: 2018-04-17
• Status Verified: 2019-05
• Study First Submitted: 2019-05-15
• Study First Submitted QC: 2019-05-15
• Last Update Submitted: 2019-05-15
• Study First Posted: 2019-05-16
• Last Update Posted: 2019-05-16
• Primary Completion: 2019-07
• Study Completion: 2019-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Absence of neurological, psychiatric, or chronic pain disorders.
• Have used at list once Ibuprofen, and not sensitive to NSAIDs.
• Ability to give informed consent, communicate, and understand the purpose and instructions of this study.

Exclusion Criteria

• Presence of diagnosed psychiatric disorders, cognitive and /or neurological deficits.
• Use of analgesic, anti-depressant or anti-enxiayoltic medications on a regular basis (except for oral contraceptives).
• Pregnancy.
• Never used NSAIDs.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Evoked pain training	Ibuprofen 400 mg	-
Control	Placebo oral tablet	-
Control	Ibuprofen 400 mg	-
Evoked pain training	Placebo oral tablet	-

Primary Outcome Measures

Name	Time	Method
Pain reporting accuracy	Fast procedure itself (49 heat stimuli, from 7 designated heat temperatures, given in a random block-order design) lasting approximately 20 minutes.	Subjects will be asked to report their pain on numerical pain scale (NPS) ranging from 0, denoting "no pain", to 10, denoting "the worst pain imaginable".
Change in experimental pain perception due to drug/placebo pill intake	Mechanical and thermal stimuli before the drug/placebo (Pre-drug/placebo) until receiving the same stimuli 40 minutes after taking the drug/placebo pill (Post-drug/placebo).	Subjects will be asked to report their pain on numerical pain scale (NPS) ranging from 0, denoting "no pain", to 10, denoting "the worst pain imaginable". The placebo effect (Δ) will be calculated as the difference between the mean NPS.

Secondary Outcome Measures

Name	Time	Method
Evoked pain training	Fast procedure itself (49 heat stimuli, from 7 designated heat temperatures, given in a random block-order design) lasting approximately 20 minutes. There are 3 training visits, each training consists of 2 FAST procedure and last approximately 1 hour.	Subjects will be asked to report their pain on numerical pain scale (NPS) ranging from 0, denoting "no pain", to 10, denoting "the worst pain imaginable".

Trial Locations

Locations (1)

University of Haifa, The Clinical Pain Innovation Lab; 🇮🇱 Haifa, Israel