Mental Effects of Analgesic Drugs: Paracetamol and Ibuprofen (MEAD)

Double Blinded Randomized Placebo Controlled Study on Mental Effects of Analgesic Drugs

The objective of the present study is to study paracetamol effects on social pain and empathy under standardized international conditions (ICH-GCP) for planning, conduction and reporting of clinical pharmaceutical studies in humans. The study included MRI imaging of brain activity, analysis of genomic biomarkers potentially explaining interindividual variation. It is controversial whether the effects are of immediate nature or develop during a period of about 10 days. Therefore, the study is separated into two study phases. Single dosing (SD) is applied in study phase 1 and multiple-dosing (MD) in study phase 2. The study compares paracetamol with placebo and in the study phase 1 also with ibuprofen as analgetically active control.

Study Overview

• Status: Unknown
• Conditions: Empathy
• Intervention / Treatment: Drug: Paracetamol; Drug: Ibuprofen; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jürgen Brockmöller, Prof.; Phone Number: +49 (0) 551 39-53 11; Email: jbrockm@gwdg.de
• Study Contact Backup: Name: Johannes Matthaei, Dr.med.; Email: matthaei.j@googlemail.com

Study Locations

• Germany
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
      • Recruiting
      • Universitatsmedizin Gottingen
      • Contact: Jürgen Brockmöller, Prof.; Phone Number: +49(0)551 39 5311; Email: jbrockm@gwdg.de
      • Contact: Alexandra Sachkova; Phone Number: +4917627786662; Email: alexandra.sachkova@med.uni-goettingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent obtained prior to study.
2. Willingness to meet the study instructions and to co-operate with the study personal.
3. No clinically relevant pathological findings in any of the investigations at the screening visit; minor deviations of laboratory values from the normal range may be accepted if judged by the investigator to have no clinical relevance.
4. Body weight not less than 48 kg and body mass index (BMI) not less than 17 kg/m² and not greater than 32 kg/m².

Exclusion Criteria:

1. Pacemaker devices, implantable or external ones.
2. Involvement in the planning and conduct of the study (applies to staff directly employed at the study site / department).
3. Known pregnancy or lactation period.
4. History of alcohol and / or drug abuse and / or any abusive use of medicaments.
5. Any disease affecting liver or kidney or impairment of the liver or kidney-function.
6. History of severe hypersensitivity reactions, anaphylaxis, psychiatric or neurologic disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paracetamol; Study phase 1 (single dosing): 1000 mg once. Study phase 2 (multiple dosing): 1000 mg twice daily for a minimum of 12 and a maximum of 14 days.	Drug: Paracetamol; Paracetamol oral tablet; Other Names: Acetaminophen
Active Comparator: Ibuprofen; Study phase 1 (single dosing): 800 mg once.	Drug: Ibuprofen; Ibuprofen oral tablet
Placebo Comparator: Placebo; Study phase 1 (single dosing): Once. Study phase 2 (multiple dosing): Twice daily for a minimum of 12 and a maximum of 14 days.	Drug: Placebo oral tablet; Sugar pill manufactured to mimic the Paracetamol and Ibuprofen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of paracetamol and ibuprofen on social pain and empathy	Primary outcome is defined as the composite score of standardized emotional scenarios and the hurt feeling scale.	8 hours
Effect of paracetamol on social pain and empathy	Primary outcome is defined as the composite score of standardized emotional scenarios and the hurt feeling scale.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychological effects of paracetamol and ibuprofen	Interindividual variation of analgesic effects measured using fMRI. MRI will be performed to reflect differences in brain activation by Psychometric test.	8 hours
Pharmacokinetics effects of paracetamol and ibuprofen	Blood samples for determination of study drug concentrations in plasma will be taken at different time-point. This will be used to calculate Maximum Plasma Concentration (Cmax).	8 hours
Pharmacogenes roles in paracetamol and ibuprofen metabolism	Genetic analysis of relevant genes responsible for paracetamol and ibuprofen Absorption, Distribution, Metabolism and Excretion (ADME).Healthy volunteers will provide a blood sample for molecular genetic analyses of the various candidate genes, e.g. drug transporters and metabolizing enzymes. This will shed light on the interindividual variation of analgesic effects.	8 hours
Psychological effects of paracetamol	Interindividual variation of analgesic effects measured using fMRI. MRI will be performed to reflect differences in brain activation by Psychometric test.	14 days
Pharmacokinetics effects of paracetamol	Blood samples for determination of study drug concentrations in plasma will be taken at different time-point. This will be used to calculate Maximum Plasma Concentration (Cmax).	14 days
Pharmacogenes roles in paracetamol metabolism	Genetic analysis of relevant genes responsible for paracetamol Absorption, Distribution, Metabolism and Excretion (ADME). Healthy volunteers will provide a blood sample for molecular genetic analyses of the various candidate genes, e.g. drug transporters and metabolizing enzymes. This will shed light on the interindividual variation of analgesic effects.	14 days

Collaborators and Investigators

• Sponsor: Prof. Jürgen Brockmöller
• Collaborators: University Hospital Ulm

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2019
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 5, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Mental effects; Social Pain
• 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; Antipyretics; Acetaminophen; Ibuprofen
• Other Study ID Numbers: 2018-004187-60

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No