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

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.

Study Overview

• Status: Unknown
• Conditions: Healthy; Placebo Response
• Intervention / Treatment: Drug: Ibuprofen 400 mg; Drug: Placebo oral tablet

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Roi Treister, PhD; Phone Number: 972-(0)4-6146214; Email: treister.roi@gmail.com
• Study Contact Backup: Name: Liat Honigman, PhD; Phone Number: 972-(0)4-6146214; Email: taliathonigman@gmail.com

Study Locations

• Israel
  • Haifa, Israel, 3498838
    • Recruiting
    • University of Haifa, The Clinical Pain Innovation Lab
    • Contact: Roi Treister, PhD; Phone Number: 972-(0)4-6146214; Email: treister.roi@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control	Drug: Ibuprofen 400 mg; Each subject will receive Ibuprofen once, in between two psycho-physical assessments. Between the drug intake and the second assessment the subject will have to wait for 40 minutes.; Drug: Placebo oral tablet; Each subject will receive Placebo (sugar pill) once, in between two psycho-physical assessments. Between the placebo pill intake and the second assessment the subject will have to wait for 40 minutes.
Experimental: Evoked pain training	Drug: Ibuprofen 400 mg; Each subject will receive Ibuprofen once, in between two psycho-physical assessments. Between the drug intake and the second assessment the subject will have to wait for 40 minutes.; Drug: Placebo oral tablet; Each subject will receive Placebo (sugar pill) once, in between two psycho-physical assessments. Between the placebo pill intake and the second assessment the subject will have to wait for 40 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain reporting accuracy	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".	Fast procedure itself (49 heat stimuli, from 7 designated heat temperatures, given in a random block-order design) lasting approximately 20 minutes.
Change in experimental pain perception due to drug/placebo pill intake	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.	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).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evoked pain training	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".	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.

Collaborators and Investigators

• Sponsor: University of Haifa

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2018
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Actual): May 16, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Placebo effect; Focus analgesia selection test (FAST); Experimental pain variability; Evoked pain training (EPT)
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: 016/18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No