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)

A Phase 4 study testing Paracetamol in people with Osteoarthritis, Knee, run by GlaxoSmithKline at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

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. Read more about this study

Who is it for?: Ages 45 years and older
Conditions the study is for: Osteoarthritis, Knee
What is being tested?: Paracetamol
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 1 siteSpain
Study dates: 1 Sep 2010to 1 Aug 2011
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 45 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Spain1 site

Hospital Del Mar
Barcelona, CP: 08003

Other trials in Spain

About this study

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

Read the 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.

Conditions: Osteoarthritis, Knee
Being tested: Paracetamol, Placebo
Keywords: osteoarthritis, pain, paracetamol, Blood-Oxygen-Level-Dependent functional magnetic resonance imaging
Medical subject headings: Osteoarthritis, Knee, Osteoarthritis, Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ParacetamolDrug
665 mg sustained release paracetamol caplets
PlaceboDrug
Placebo caplets

Study groups in NCT01105936
Study group	Role	What they receive
Paracetamol caplets	Experimental	Two 665 mg sustained release paracetamol caplets administered orally with water. Receives: Drug: Paracetamol
Placebo caplets	Placebo comparator	Two placebo caplets administered orally with water. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline to 2-5 hours post last dose administration

Secondary outcomes (6)

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
Measured: 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)]
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".
Measured: 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)]
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".
Measured: 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)]
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".
Measured: 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)]
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".
Measured: 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)]
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".
Measured: Baseline and post-dose post-scan after stimulus

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 20101 Aug 2011

First posted19 Apr 2010 (estimated)
Study start1 Sep 2010
Primary completion1 Aug 2011
Study completion1 Aug 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01105936
Sponsor's protocol ID: A3360529
Status last verified: May 2017
First submitted: 4 Mar 2010
Last updated: 21 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Chronic Pain Master Protocol (CPMP): A Study of LY4065967 in Participants With Osteoarthritis Pain
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EFFECT OF ADDING BLOOD FLOW RESTRICTION TRAINING TO CLOSED CHAIN EXERCISE IN KNEE OSTEOARTHRITIS
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Platelet-Rich Plasma, Hyaluronic Acid, or Their Combination for Knee Osteoarthritis in Athletes
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All Osteoarthritis, Knee trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-blind, Evaluation of the Effects of Paracetamol on the BOLD fMRI Response to Painful Stimuli in Subjects With Osteoarthritis
ClinicalTrials.gov ID: NCT01105936
Acronym / sponsor ID: A3360529
Conditions: Osteoarthritis, Knee
Keywords: osteoarthritis, pain, paracetamol, Blood-Oxygen-Level-Dependent functional magnetic resonance imaging
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 31 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 1 Sep 2010
Primary completion: 1 Aug 2011 (actual)
Study completion: 1 Aug 2011 (actual)
First posted: 19 Apr 2010 (estimated)
Results: Posted 24 Mar 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Paracetamol caplets	Experimental	Drug: ParacetamolTwo 665 mg sustained release paracetamol caplets administered orally with water.
Placebo caplets	Placebo comparator	Drug: PlaceboTwo placebo caplets administered orally with water.

Who may qualify

Ages: 45 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Paracetamol665 mg sustained release paracetamol caplets	Drug	Paracetamol caplets
PlaceboPlacebo caplets	Drug	Placebo caplets

Primary outcome

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.

6 secondary outcomes

BOLD Response in the Patello-femoral Joint of Knee Osteoarthritis: [BOLD (P-f)]
Time frame: 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 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 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 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 Patello-femoral Stimulation After the fMRI Scan: [NRS (P-f Post-scan)]
Time frame: Baseline and post-dose post-scan after stimulus

Results and safety

Results posted to the registry on 24 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence 1	8	8
Sequence 2	8	8
Sequence 3	7	7
Sequence 4	8	7

Primary outcome: 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. Mean (Standard Deviation). Unit: Z-score

Measure	Paracetamol 665 mg n = 20	Placebo n = 23	No Treatment n = 23
Value	NA (NA)	NA (NA)	NA (NA)

Population analysed: 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.

6 secondary outcomes are reported in the full results.

Adverse events

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.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Paracetamol 665 mg	0 of 29 (0%)	3 of 29 (10.3%)	Not reported
Placebo	0 of 28 (0%)	3 of 28 (10.7%)	Not reported
No Treatment	0 of 30 (0%)	2 of 30 (6.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Osteoarthritis, Knee

RecruitingPhase 2
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EFFECT OF ADDING BLOOD FLOW RESTRICTION TRAINING TO CLOSED CHAIN EXERCISE IN KNEE OSTEOARTHRITIS
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Paracetamol in people with Osteoarthritis, Knee, run by GlaxoSmithKline at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01105936.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2017.