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)

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01105936
• Other study ID #: A3360529
• Status: Completed
• Phase: Phase 4
• First received: March 4, 2010
• Last updated: March 26, 2015
• Start date: September 2010
• Est. completion date: August 2011

Study information

• Verified date: March 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Paracetamol
665 mg sustained release paracetamol caplets
• Placebo
Placebo caplets

Locations

Country	Name	City	State
Spain	Hospital Del Mar	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Oxygen Level-Dependent (BOLD) Response in the Tibio-femoral Joint of Knee Osteoarthritis (OA): [BOLD (T-f)]	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	No
Secondary	BOLD Response in the Patello-femoral Joint of Knee Osteoarthritis: [BOLD (P-f)]	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	No
Secondary	Subjective Numerical Rating Scale (NRS) Response for Treatment Effect on OA Knee Before Stimulation: [NRS (TRT)]	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	No
Secondary	Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation Prior the fMRI Scan: [NRS (T-f Pre-scan)]	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	No
Secondary	Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation Prior the fMRI Scan: [NRS (P-f Pre-scan)]	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	No
Secondary	Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation After the fMRI Scan: [NRS (T-f Post-scan)]	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	No
Secondary	Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation After the fMRI Scan: [NRS (P-f Post-scan)]	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	No