ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Basic Science
Condition Osteoarthritis, Knee
Interventions Drug: Paracetamol
Drug: Placebo
Enrollment 31
Recruitment Details Study was conducted at a single centre in Spain.
Pre-assignment Details Out of 33 screened participants, 31 were randomized, while 2 participants were considered as screen failures
Arm/Group Title Sequence 1 Sequence 2 Sequence 3 Sequence 4
Hide Arm/Group Description Participants took part in 3 study sessions. Session 1-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 2-no treatment was given. Session 3-participant took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3. Participants took part in 3 study sessions. Session 1-participants took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 2-no treatment was given. Session 3-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3. Participants took part in 3 study sessions. Session 1-no treatment was given. Session 2-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 3-participants took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered.A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3. Participants took part in 3 study sessions. Session 1-no treatment was given. Session 2-participants took two caplets of matched placebo orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. Session 3-participant took two 665 mg sustained release paracetamol formulations orally with 150 ml water. Four consecutive doses were administered every 8h, with the first dose (0h) and last dose (24h) under supervision at clinic and the second dose (8h) and third dose (16h) self-administered. A 5-14 day washout was given after session 1 and session 2. A 7-14 day follow-up was done after session 3.
Period Title: Period 1
Started 8 8 7 8
Completed 8 8 7 7
Not Completed 0 0 0 1
Reason Not Completed
Adverse Event             0             0             0             1
Period Title: Wash-out Period 1
Started 8 8 7 7
Completed 8 8 7 7
Not Completed 0 0 0 0
Period Title: Period 2
Started 8 8 7 7
Completed 7 8 7 7
Not Completed 1 0 0 0
Reason Not Completed
Adverse Event             1             0             0             0
Period Title: Wash-out Period 2
Started 7 8 7 7
Completed 7 8 7 7
Not Completed 0 0 0 0
Period Title: Period 3
Started 7 8 7 7
Completed 7 6 7 7
Not Completed 0 2 0 0
Reason Not Completed
Protocol Violation             0             2             0             0
Arm/Group Title Total Participants for Baseline Measurement
Hide Arm/Group Description All randomized participants except one were evaluated for baseline measures. One participant had misallocated treatments that could not be determined. Therefore, this participant was excluded from all populations including safety.
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Years Number Analyzed 30 participants
68.5  (7.97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
26
  86.7%
Male
4
  13.3%
1.Primary Outcome
Title Blood Oxygen Level-Dependent (BOLD) Response in the Tibio-femoral Joint of Knee Osteoarthritis (OA): [BOLD (T-f)]
Hide Description 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.
Time Frame Baseline to 2-5 hours post last dose administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed.
Arm/Group Title Paracetamol 665 mg Placebo No Treatment
Hide Arm/Group Description:
Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water.
Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water.
No treatment was given to participants.
Overall Number of Participants Analyzed 20 23 23
Mean (Standard Deviation)
Unit of Measure: Z-score
NA [1]   (NA) NA [2]   (NA) NA [3]   (NA)
[1]
BOLD value had no detectable signal for Paracetamol 665 mg group.
[2]
BOLD value had no detectable signal for Placebo group.
[3]
BOLD value had no detectable signal for No Treatment group.
2.Secondary Outcome
Title BOLD Response in the Patello-femoral Joint of Knee Osteoarthritis: [BOLD (P-f)]
Hide Description 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
Time Frame Baseline to 2-5 hours post last dose administration
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed.
Arm/Group Title Paracetamol 665 mg Placebo No Treatment
Hide Arm/Group Description:
Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water.
Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water.
No treatment was given to participants.
Overall Number of Participants Analyzed 20 23 23
Mean (Standard Deviation)
Unit of Measure: Z-score
BOLD - Sensory Cortex (a) 0.16  (0.36) NA [1]   (NA) 0.48  (0.48)
BOLD - Supramarginal Gyrus 0.46  (0.48) NA [2]   (NA) 0.76  (0.49)
BOLD - Thalamus 0.48  (1.34) -0.68  (1.74) NA [3]   (NA)
BOLD - Subgenu Prefrontal NA [4]   (NA) -0.27  (0.41) 0.19  (0.37)
BOLD - Frontal Cortex NA [5]   (NA) -0.04  (0.31) 0.26  (0.42)
BOLD - Insula NA [6]   (NA) 0.12  (0.51) 0.62  (0.62)
BOLD - Sensory Cortex (b) NA [7]   (NA) -0.11  (0.60) 0.44  (0.48)
[1]
BOLD - Sensory Cortex (a) value had no detectable signal for Placebo Group.
[2]
BOLD - Supramarginal Gyrus value had no detectable signal for Placebo Group.
[3]
BOLD - Thalamus value had no detectable signal for No treatment group.
[4]
BOLD - Subgenu Prefrontal value had no detectable signal for Paracetamol 665 mg group.
[5]
BOLD - Frontal Cortex value had no detectable signal for Paracetamol 665 mg group.
[6]
BOLD - Insula value had no detectable signal for Paracetamol 665 mg group.
[7]
BOLD - Sensory Cortex (b) value had no detectable signal for Paracetamol 665 mg group.
3.Secondary Outcome
Title Subjective Numerical Rating Scale (NRS) Response for Treatment Effect on OA Knee Before Stimulation: [NRS (TRT)]
Hide Description 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”.
Time Frame Baseline and post-dose before stimulus
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed.
Arm/Group Title Paracetamol 665 Milligram (mg) Placebo No Treatment
Hide Arm/Group Description:
Participants took two 665 mg Paracetamol sustained release caplets orally with 150mL of water.
Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water.
No treatment was given to participants.
Overall Number of Participants Analyzed 20 23 23
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
0.95  (1.67) -0.52  (1.53) 0.48  (1.83)
4.Secondary Outcome
Title Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation Prior the fMRI Scan: [NRS (T-f Pre-scan)]
Hide Description 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”.
Time Frame Baseline and post-dose pre-scan after stimulus
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed.
Arm/Group Title Paracetamol 665 mg Placebo No Treatment
Hide Arm/Group Description:
Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water.
Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water.
No treatment was given to participants.
Overall Number of Participants Analyzed 20 23 23
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
0.55  (0.89) 0.17  (1.07) 0.00  (0.74)
5.Secondary Outcome
Title Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation Prior the fMRI Scan: [NRS (P-f Pre-scan)]
Hide Description 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”.
Time Frame Baseline and post-dose pre-scan after stimulus
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed.
Arm/Group Title Paracetamol 665 mg Placebo No Treatment
Hide Arm/Group Description:
Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water.
Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water.
No treatment was given to participants.
Overall Number of Participants Analyzed 20 23 23
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
0.60  (1.23) 0.43  (0.95) 0.00  (0.91)
6.Secondary Outcome
Title Subjective NRS Response for Treatment Effect on Tibio-femoral Stimulation After the fMRI Scan: [NRS (T-f Post-scan)]
Hide Description 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”.
Time Frame Baseline and post-dose post-scan after stimulus
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed.
Arm/Group Title Paracetamol 665 mg Placebo No Treatment
Hide Arm/Group Description:
Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water.
Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water.
No treatment was given to participants.
Overall Number of Participants Analyzed 20 23 23
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
0.15  (1.18) 0.09  (1.38) -0.13  (1.10)
7.Secondary Outcome
Title Subjective NRS Response for Treatment Effect on Patello-femoral Stimulation After the fMRI Scan: [NRS (P-f Post-scan)]
Hide Description 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”.
Time Frame Baseline and post-dose post-scan after stimulus
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population: all participants per period who received at least one treatment and had at least one post-baseline efficacy assessment. Missing data was not imputed.
Arm/Group Title Paracetamol 665 mg Placebo No Treatment
Hide Arm/Group Description:
Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water.
Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water.
No treatment was given to participants.
Overall Number of Participants Analyzed 20 23 23
Mean (Standard Deviation)
Unit of Measure: Score on a Scale
0.30  (1.66) -0.48  (1.62) -0.39  (1.92)
Time Frame Adverse Events were collected from the time of start of the investigational product, and until 5 days following last administration of the investigational product.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Paracetamol 665 mg Placebo No Treatment
Hide Arm/Group Description Participants took two 665 mg Paracetamol sustained release caplets orally with 150 mL of water. Participants took two placebo caplets to match Paracetamol sustained release caplets orally with 150 mL of water. No treatment was given to participants.
All-Cause Mortality
Paracetamol 665 mg Placebo No Treatment
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Paracetamol 665 mg Placebo No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/29 (0.00%)      0/28 (0.00%)      0/30 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Paracetamol 665 mg Placebo No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/29 (10.34%)      3/28 (10.71%)      2/30 (6.67%)    
Gastrointestinal disorders       
Dental caries   1/29 (3.45%)  1 0/28 (0.00%)  0 0/30 (0.00%)  0
Diarrhoea   0/29 (0.00%)  0 1/28 (3.57%)  1 0/30 (0.00%)  0
Injury, poisoning and procedural complications       
Laceration   0/29 (0.00%)  0 0/28 (0.00%)  0 1/30 (3.33%)  1
Musculoskeletal and connective tissue disorders       
Bone Pain   1/29 (3.45%)  1 0/28 (0.00%)  0 0/30 (0.00%)  0
Nervous system disorders       
Headache   0/29 (0.00%)  0 1/28 (3.57%)  1 0/30 (0.00%)  0
Psychiatric disorders       
Anxiety   1/29 (3.45%)  1 1/28 (3.57%)  1 0/30 (0.00%)  0
Claustrophobia   0/29 (0.00%)  0 0/28 (0.00%)  0 1/30 (3.33%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01105936     History of Changes
Other Study ID Numbers: A3360529
First Submitted: March 4, 2010
First Posted: April 19, 2010
Results First Submitted: June 20, 2013
Results First Posted: March 24, 2015
Last Update Posted: June 21, 2017