Mental Effects of Analgesic Drugs: Paracetamol and Ibuprofen

Study Overview
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Brief Summary
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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.

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

Conditions
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Empathy

Intervention / Treatment
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* Drug: Paracetamol
* Drug: Ibuprofen
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained prior to study. Willingness to meet the study instructions and to co-operate with the study personal. 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. 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: Pacemaker devices, implantable or external ones. Involvement in the planning and conduct of the study (applies to staff directly employed at the study site / department). Known pregnancy or lactation period. History of alcohol and / or drug abuse and / or any abusive use of medicaments. Any disease affecting liver or kidney or impairment of the liver or kidney-function. History of severe hypersensitivity reactions, anaphylaxis, psychiatric or neurologic disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective with placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paracetamol<br>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<br>* Paracetamol oral tablet<br>* Other names: Acetaminophen;|
| Active Comparator: Ibuprofen<br>Study phase 1 (single dosing): 800 mg once. | Drug: Ibuprofen<br>* Ibuprofen oral tablet<br>|
| Placebo Comparator: Placebo<br>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<br>* Sugar pill manufactured to mimic the Paracetamol and Ibuprofen.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mental effects, Social Pain