Assess the Blood-Oxygen-Level-Dependent (BOLD) Signal Changes in the Brain by Paracetamol as Measured by Functional Magnetic Resonance Imaging (fMRI) in Subjects With Osteoarthritis (OA)

May 29, 2017 updated by: GlaxoSmithKline

A Randomised, Double-blind, Evaluation of the Effects of Paracetamol on the BOLD fMRI Response to Painful Stimuli in Subjects With Osteoarthritis

Blood-Oxygen-Level-Dependent (BOLD) responses to painful mechanical stimulation of the OA knee following treatment with four consecutive doses (at 8 hour intervals) on giving sustained released paracetamol treatment or placebo will be compared. The fMRI and pain assessments will occur approximately 2-5 hours after taking the final dose.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The objective of this study is to investigate if functional magnetic response imaging (fMRI) can detect the effects of a known pain medicine at over-the-counter doses in people with osteoarthritis (OA) of the knee. The fMRI is a harmless and painless technique that is used in the current study to collect images of brain activity to see if is changed when feeling pain. In this study, BOLD response to mechanical stimulation via pressure stimuli applied to the tibio-femoral joint and patello-femoral in participants with knee OA following four treatment doses of any of three treatment will be compared.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Barcelona, Spain, CP: 08003
        • Hospital Del Mar

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of osteoarthritis of at least one knee for 3 months
  • Male or female at least 45 years of age
  • Score a minimum of 4 out of 10 on the numerical pain rating and a maximum of 8 at screening

Exclusion Criteria:

  • If female, is pregnant, lactating, or breast feeding
  • Has secondary cause of knee arthritis
  • Lower extremity surgery in the last 6 months
  • Prior injury in the last twelve months to the index knee
  • Used any analgesics (NSAIDs, COX2 inhibitor, etc) within 5 half lives of study start
  • Recently used oral or injected glucocorticoids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Paracetamol caplets
Two 665 mg sustained release paracetamol caplets administered orally with water.
Drug: Paracetamol
665 mg sustained release paracetamol caplets
PLACEBO_COMPARATOR: Placebo caplets
Two placebo caplets administered orally with water.
Drug: Placebo
Placebo caplets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood Oxygen Level-Dependent (BOLD) Response in the Tibio-femoral Joint of Knee Osteoarthritis (OA): [BOLD (T-f)]
Time Frame: Baseline to 2-5 hours post last dose administration
BOLD response to painful pressure stimuli was evaluated using fMRI. Voxel-wise BOLD scores were reported on a Z-scale (Gaussian,mean=0,SD=1); range -3 (worst score, lowest connectivity) to +3 (best score, highest connectivity). The software derived scores compared the intensity reading in the region to a template, specifically the Montreal Neurological Institute (MNI) Echo-Planar Image (EPI) template. The template provides, for each region, expected (mean/median) intensity for that region, along with expected variation. The BOLD score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution.
Baseline to 2-5 hours post last dose administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
BOLD Response in the Patello-femoral Joint of Knee Osteoarthritis: [BOLD (P-f)]
Time Frame: Baseline to 2-5 hours post last dose administration
BOLD response to painful pressure stimuli was evaluated using fMRI. Voxel-wise BOLD scores were reported on a Z-scale (Gaussian,mean=0,SD=1); range -3 (worst score, lowest connectivity) to +3 (best score, highest connectivity). The software derived scores compared the intensity reading in the region to a template, specifically the Montreal Neurological Institute (MNI) Echo-Planar Image (EPI) template. The template provides, for each region, expected (mean/median) intensity for that region, along with expected variation. The BOLD score on the Z-scale represents how far the actual measured intensity is from the expected in the template. A score of 0 would correspond to the mean/median, a score of 1.65 would represent the 90-percentile, -1.65 the 10-percentile, and so on, according to a standard normal distribution
Baseline to 2-5 hours post last dose administration
Subjective Numerical Rating Scale (NRS) Response for Treatment Effect on OA Knee Before Stimulation: [NRS (TRT)]
Time Frame: Baseline and post-dose before stimulus
Subjective NRS response for each participant was calculated as difference of pre-treatment NRS pain assessment before stimulus and post-treatment NRS pain assessment before stimulus. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine".
Baseline and post-dose before stimulus
Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation Prior the fMRI Scan: [NRS (T-f Pre-scan)]
Time Frame: Baseline and post-dose pre-scan after stimulus
Subjective NRS response was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment pre-scan pain assessment after stimulus on tibio-femoral joint. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine".
Baseline and post-dose pre-scan after stimulus
Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation Prior the fMRI Scan: [NRS (P-f Pre-scan)]
Time Frame: Baseline and post-dose pre-scan after stimulus
Subjective NRS response was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment pre-scan pain assessment after stimulus on patello-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine".
Baseline and post-dose pre-scan after stimulus
Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation After the fMRI Scan: [NRS (T-f Post-scan)]
Time Frame: Baseline and post-dose post-scan after stimulus
Subjective NRS response for treatment effect on tibio-femoral stimulus after the fMRI scan was calculated for each participant as difference of pre-treatment pain assessment after stimulus and post-treatment post-scan pain assessment after stimulus on tibio-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine".
Baseline and post-dose post-scan after stimulus
Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation After the fMRI Scan: [NRS (P-f Post-scan)]
Time Frame: Baseline and post-dose post-scan after stimulus
Subjective NRS response for each participant for treatment effect on tibio-femoral stimulus after the fMRI scan was calculated as difference of pre-treatment pain assessment after stimulus and post-treatment post-scan pain assessment after stimulus on patello-femoral. NRS responses was based on an 11 scale rating (0-10), with 0 corresponding to "No Pain" and 10 corresponding to "Extreme Pain or Pain as bad as you can imagine".
Baseline and post-dose post-scan after stimulus

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (ACTUAL)

August 1, 2011

Study Completion (ACTUAL)

August 1, 2011

Study Registration Dates

First Submitted

March 4, 2010

First Submitted That Met QC Criteria

April 15, 2010

First Posted (ESTIMATE)

April 19, 2010

Study Record Updates

Last Update Posted (ACTUAL)

June 21, 2017

Last Update Submitted That Met QC Criteria

May 29, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A3360529

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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