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)

• ClinicalTrials.gov Identifier: NCT01105936
• Recruitment Status: Completed
• First Posted: April 19, 2010
• Results First Posted: March 24, 2015
• Last Update Posted: June 21, 2017
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee	Drug: Paracetamol; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Randomised, Double-blind, Evaluation of the Effects of Paracetamol on the BOLD fMRI Response to Painful Stimuli in Subjects With Osteoarthritis
• Study Start Date: September 1, 2010
• Actual Primary Completion Date: August 1, 2011
• Actual Study Completion Date: August 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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
2. 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".
3. 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".
4. 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".
5. 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".
6. 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".

Eligibility Criteria

• Ages Eligible for Study: 45 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Spain

Hospital Del Mar

Barcelona, Spain, CP: 08003

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01105936
• Other Study ID Numbers: A3360529
• First Posted: April 19, 2010
• Results First Posted: March 24, 2015
• Last Update Posted: June 21, 2017
• Last Verified: May 2017

Keywords provided by GlaxoSmithKline:

osteoarthritis; pain; paracetamol; Blood-Oxygen-Level-Dependent functional magnetic resonance imaging

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Acetaminophen; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics