Knee OsteoarthritisPhase 2/3TOPICALNCT03199417
Trial Evaluating multimOdal toPical Cream In CompArison to pLacebo (TOPICAL)
A Phase 2/3 study testing Multiprofen in people with Knee Osteoarthritis, run by University of Michigan at 1 site in Canada.
Trial summary
Randomized controlled trial regarding the efficacy of a multimodal topical analgesic, Multiprofen, in comparison to placebo cream treatment on knee pain and function in patients with knee osteoarthritis. Read more about this study
- Who is it for?
- Ages 50 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- Multiprofen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- 1 May 2017to 30 May 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 50 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The inclusion criteria are:
- adult men or women ages 50-80 years;
- Diagnosis of symptomatic osteoarthritis of the knee based on clinical and radiographic criteria;
- provision of informed consent.
Who cannot join
- The exclusion criteria are:
- patients with inflammatory osteoarthritis;
- open wounds or sores over the knee joint;
- patients that will likely have problems, in the judgment of the investigators, with maintaining follow-up;
- Cases involving litigation.
Trial locations and contacts
1 site in 1 country.
About this study
Randomized controlled trial regarding the efficacy of a multimodal topical analgesic, Multiprofen, in comparison to placebo cream treatment on knee pain and function in patients with knee osteoarthritis.
Read the detailed description
Knee osteoarthritis (OA) is a disease with a high global burden, and multiple conservative treatment options are available. In addition to being a major source of disability osteoarthritis results in a significant economic burden as well. A study published in 2012 showed the 1-year physician, outpatient procedure, and hospitalization costs in patients with osteoarthritis more than double those patients without osteoarthritis in Ontario.
Conservative treatment options include topical and oral anti-inflammatory medications, weight loss, physiotherapy and intra articular cortisone and viscosupplementation injections. Unfortunately, commonly used treatments such as oral anti-inflammatory medications carry a significant systemic adverse effect on the gastrointestinal (GI) tract and hepatic and renal systems and intra articular cortisone have potential adverse effect on blood glucose control. For this reason, topical anti-inflammatory medications are popular yet are often ineffective. Unfortunately, topical anti-inflammatory medications have variable efficacy in relieving osteoarthritic knee pain and often only provide a moderate degree of pain relief.
In the setting of chronic pain various other topical modalities have been utilized. A systematic review of the literature identified commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs followed by lidocaine, capsaicin, amitriptyline, glyceryl trinitrate, opioids, menthol, pimecrolimus, and phenytoin. Given the biological bases behind utilizing agents which target a variety of pain generators the investigators hypothesized that a combination of these would provide significant pain relief to patients affected by end stage knee osteoarthritis. For this reason, the investigators propose a trial evaluating utilizing multiple topical modalities for pain relief to provide support for the use of combination therapy in treating knee osteoarthritis. Results from this study will potentially improve the global health and economic burden through improvement in the management of knee osteoarthritis.
STUDY OBJECTIVES
Primary objective The primary objective of the trial will be to evaluate the efficacy of a multimodal topical analgesic, Multiprofen, in comparison to placebo cream treatment on patient reported pain relief utilizing a 11-point visual analog scale (VAS) measured from 0-10.
Secondary objectives
Our secondary objectives will be to evaluate the effect of topical combination therapy on:
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) patient reported outcome score. This score is commonly utilized in assessment of knee osteoarthritis and has been validated to be reliable and responsive in this patient population.
- Patient knee range of motion and strength
- Return to previous level of activity
- Radiographic degree of osteoarthritis.
- Patient demographics
- Adverse events
SUMMARY OF TRIAL DESIGN The investigators propose a single center blinded trial evaluating the efficacy of a combination formula of topical analgesic in comparison to placebo cream treatment. The investigators will randomize 186 patients between topical multimodal cream "multiprofen" and a control placebo cream.
Randomization Method Participants will be randomized using a random number generator to either experimental or placebo control intervention.
Participants will be randomized to one of two treatments:
Experimental - A multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel. This topical formulation has been in use commercially under the trade name "Multi-profen".
Control - A identically packaged placebo cream treatment will be utilized in the control population.
Proposed duration of treatment and follow-up: Participants will be brought back at 3,6 and 12 weeks' time to complete questionnaires recording VAS and WOMAC scores
The current proposal includes 1 clinical site in Canada (Oakville Trafalgar Memorial Hospital, Oakville, ON, CAN)
- Conditions
- Knee Osteoarthritis
- Being tested
- Multiprofen, Placebo
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MultiprofenDrug
A multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel.
PlaceboOther
An identically packaged placebo cream
| Study group | Role | What they receive |
|---|---|---|
| Multiprofen/interventional | Experimental | A multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel. This topical formulation has been in use commercially under the trade name "Multi-profen". This topical cream will be applied by the patient three times per day. Receives: Drug: Multiprofen |
| Control/Placebo Group | Placebo comparator | A identically packaged placebo cream treatment will be utilized in the control population. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pain visual analog scale (VAS) scores (0-10) from baseline
Measurement of change in patient reported pain score (VAS) at various follow up appointments. The scale is from 0-10, with 10 being the most pain.
Measured: week 0, week 3, week 6, week 12
Secondary outcomes (2)
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from baseline
Change in patient reported knee pain and function scores. WOMAC score has 3 subdivisions which include knee pain, stiffness, and physical function. The score ranges from 0-96, with lower scores representing better knee pain, stiffness, and function.
Measured: week 0, week 3, week 6, week 12
Change in Range of motion (ROM) from baseline
Change in range of motion of the knee at various time points that will be compared to pre-treatment range of motion. Higher range of motion is correlated with better outcome and better function.
Measured: week 0, week 3, week 6, week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2017
- Study start1 May 2017
- Primary completion30 May 2018
- Study completion30 May 2018
Why it stopped: Terminated prematurely due to feasibility issues with rate of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- More trials run by University of MichiganThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single center blinded randomized controlled trial with a random number generator determining the allocation of patients to either the placebo or intervention groups.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- McMaster University, Oakville Trafalgar Memorial Hospital
- Responsible party
- Principal investigator, Neil Bakshi, University of Michigan
- Investigators
- Moin Khan, MD, Principal investigator, MCMASTER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199417
- Sponsor's protocol ID
- 2017/02
- Acronym
- TOPICAL
- Status last verified
- Mar 2019
- First submitted
- 21 Jun 2017
- Last updated
- 20 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tarride JE, Haq M, O'Reilly DJ, Bowen JM, Xie F, Dolovich L, Goeree R. The excess burden of osteoarthritis in the province of Ontario, Canada. Arthritis Rheum. 2012 Apr;64(4):1153-61. doi: 10.1002/art.33467. Epub 2011 Nov 11.
PubMed 22081470Rannou F, Pelletier JP, Martel-Pelletier J. Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S18-21. doi: 10.1016/j.semarthrit.2015.11.007. Epub 2015 Dec 2.
PubMed 26806189Stanos SP, Galluzzi KE. Topical therapies in the management of chronic pain. Postgrad Med. 2013 Jul;125(4 Suppl 1):25-33. doi: 10.1080/00325481.2013.1110567111.
PubMed 24547601Argoff CE. Topical analgesics in the management of acute and chronic pain. Mayo Clin Proc. 2013 Feb;88(2):195-205. doi: 10.1016/j.mayocp.2012.11.015.
PubMed 23374622Williams VJ, Piva SR, Irrgang JJ, Crossley C, Fitzgerald GK. Comparison of reliability and responsiveness of patient-reported clinical outcome measures in knee osteoarthritis rehabilitation. J Orthop Sports Phys Ther. 2012 Aug;42(8):716-23. doi: 10.2519/jospt.2012.4038. Epub 2012 Mar 8.
PubMed 22402677Katz NP, Paillard FC, Ekman E. Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions. J Orthop Surg Res. 2015 Feb 3;10:24. doi: 10.1186/s13018-014-0144-x.
PubMed 25645576Jabbari M, Hashempur MH, Razavi SZ, Shahraki HR, Kamalinejad M, Emtiazy M. Efficacy and short-term safety of topical Dwarf Elder (Sambucus ebulus L.) versus diclofenac for knee osteoarthritis: A randomized, double-blind, active-controlled trial. J Ethnopharmacol. 2016 Jul 21;188:80-6. doi: 10.1016/j.jep.2016.04.035. Epub 2016 Apr 26.
PubMed 27125590Fernandez-Lopez JC, Laffon A, Blanco FJ, Carmona L; EPISER Study Group. Prevalence, risk factors, and impact of knee pain suggesting osteoarthritis in Spain. Clin Exp Rheumatol. 2008 Mar-Apr;26(2):324-32.
PubMed 18565256
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial Evaluating multimOdal toPical Cream In CompArison to pLacebo (TOPICAL)
- ClinicalTrials.gov ID
- NCT03199417
- Acronym / sponsor ID
- TOPICAL / 2017/02
- Conditions
- Knee Osteoarthritis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated prematurely due to feasibility issues with rate of recruitment
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- McMaster University, Oakville Trafalgar Memorial Hospital
- Study start
- 1 May 2017 (actual)
- Primary completion
- 30 May 2018 (actual)
- Study completion
- 30 May 2018 (actual)
- First posted
- 26 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized controlled trial regarding the efficacy of a multimodal topical analgesic, Multiprofen, in comparison to placebo cream treatment on knee pain and function in patients with knee osteoarthritis.
Detailed description
Knee osteoarthritis (OA) is a disease with a high global burden, and multiple conservative treatment options are available. In addition to being a major source of disability osteoarthritis results in a significant economic burden as well. A study published in 2012 showed the 1-year physician, outpatient procedure, and hospitalization costs in patients with osteoarthritis more than double those patients without osteoarthritis in Ontario.
Conservative treatment options include topical and oral anti-inflammatory medications, weight loss, physiotherapy and intra articular cortisone and viscosupplementation injections. Unfortunately, commonly used treatments such as oral anti-inflammatory medications carry a significant systemic adverse effect on the gastrointestinal (GI) tract and hepatic and renal systems and intra articular cortisone have potential adverse effect on blood glucose control. For this reason, topical anti-inflammatory medications are popular yet are often ineffective. Unfortunately, topical anti-inflammatory medications have variable efficacy in relieving osteoarthritic knee pain and often only provide a moderate degree of pain relief.
In the setting of chronic pain various other topical modalities have been utilized. A systematic review of the literature identified commonly studied topical analgesics were nonsteroidal anti-inflammatory drugs followed by lidocaine, capsaicin, amitriptyline, glyceryl trinitrate, opioids, menthol, pimecrolimus, and phenytoin. Given the biological bases behind utilizing agents which target a variety of pain generators the investigators hypothesized that a combination of these would provide significant pain relief to patients affected by end stage knee osteoarthritis. For this reason, the investigators propose a trial evaluating utilizing multiple topical modalities for pain relief to provide support for the use of combination therapy in treating knee osteoarthritis. Results from this study will potentially improve the global health and economic burden through improvement in the management of knee osteoarthritis.
STUDY OBJECTIVES
Primary objective The primary objective of the trial will be to evaluate the efficacy of a multimodal topical analgesic, Multiprofen, in comparison to placebo cream treatment on patient reported pain relief utilizing a 11-point visual analog scale (VAS) measured from 0-10.
Secondary objectives
Our secondary objectives will be to evaluate the effect of topical combination therapy on:
- Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) patient reported outcome score. This score is commonly utilized in assessment of knee osteoarthritis and has been validated to be reliable and responsive in this patient population.
- Patient knee range of motion and strength
- Return to previous level of activity
- Radiographic degree of osteoarthritis.
- Patient demographics
- Adverse events
SUMMARY OF TRIAL DESIGN The investigators propose a single center blinded trial evaluating the efficacy of a combination formula of topical analgesic in comparison to placebo cream treatment. The investigators will randomize 186 patients between topical multimodal cream "multiprofen" and a control placebo cream.
Randomization Method Participants will be randomized using a random number generator to either experimental or placebo control intervention.
Participants will be randomized to one of two treatments:
Experimental - A multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel. This topical formulation has been in use commercially under the trade name "Multi-profen".
Control - A identically packaged placebo cream treatment will be utilized in the control population.
Proposed duration of treatment and follow-up: Participants will be brought back at 3,6 and 12 weeks' time to complete questionnaires recording VAS and WOMAC scores
The current proposal includes 1 clinical site in Canada (Oakville Trafalgar Memorial Hospital, Oakville, ON, CAN)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Single center blinded randomized controlled trial with a random number generator determining the allocation of patients to either the placebo or intervention groups.
| Arm | Type | Receives |
|---|---|---|
| Multiprofen/interventional | Experimental | Drug: MultiprofenA multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel. This topical formulation has been in use commercially under the trade name "Multi-profen". This topical cream will be applied by the patient three times per day. |
| Control/Placebo Group | Placebo comparator | Other: PlaceboA identically packaged placebo cream treatment will be utilized in the control population. |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- adult men or women ages 50-80 years;
- Diagnosis of symptomatic osteoarthritis of the knee based on clinical and radiographic criteria;
- provision of informed consent.
Key exclusion criteria (5 listed)
- patients with inflammatory osteoarthritis;
- open wounds or sores over the knee joint;
- patients that will likely have problems, in the judgment of the investigators, with maintaining follow-up;
- Cases involving litigation.
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 |
|---|---|---|
| MultiprofenA multimodal topical cream treatment with Ketoprofen, Baclofen, Amitryptiline, and lidocaine in a carrier gel. | Drug | Multiprofen/interventional |
| PlaceboAn identically packaged placebo cream | Other | Control/Placebo Group |
Primary outcome
Change in pain visual analog scale (VAS) scores (0-10) from baseline
Time frame: week 0, week 3, week 6, week 12
Measurement of change in patient reported pain score (VAS) at various follow up appointments. The scale is from 0-10, with 10 being the most pain.
2 secondary outcomes
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from baseline
Time frame: week 0, week 3, week 6, week 12
Change in Range of motion (ROM) from baseline
Time frame: week 0, week 3, week 6, week 12
Results and safety
The study was stopped early (reason given: Terminated prematurely due to feasibility issues with rate of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2019.
- Background: PubMed 22081470Tarride JE, Haq M, O'Reilly DJ, Bowen JM, Xie F, Dolovich L, Goeree R. The excess burden of osteoarthritis in the province of Ontario, Canada. Arthritis Rheum. 2012 Apr;64(4):1153-61. doi: 10.1002/art.33467. Epub 2011 Nov 11.
- Background: PubMed 26806189Rannou F, Pelletier JP, Martel-Pelletier J. Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys. Semin Arthritis Rheum. 2016 Feb;45(4 Suppl):S18-21. doi: 10.1016/j.semarthrit.2015.11.007. Epub 2015 Dec 2.
- Background: PubMed 24547601Stanos SP, Galluzzi KE. Topical therapies in the management of chronic pain. Postgrad Med. 2013 Jul;125(4 Suppl 1):25-33. doi: 10.1080/00325481.2013.1110567111.
- Background: PubMed 23374622Argoff CE. Topical analgesics in the management of acute and chronic pain. Mayo Clin Proc. 2013 Feb;88(2):195-205. doi: 10.1016/j.mayocp.2012.11.015.
- Background: PubMed 22402677Williams VJ, Piva SR, Irrgang JJ, Crossley C, Fitzgerald GK. Comparison of reliability and responsiveness of patient-reported clinical outcome measures in knee osteoarthritis rehabilitation. J Orthop Sports Phys Ther. 2012 Aug;42(8):716-23. doi: 10.2519/jospt.2012.4038. Epub 2012 Mar 8.
- Background: PubMed 25645576Katz NP, Paillard FC, Ekman E. Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions. J Orthop Surg Res. 2015 Feb 3;10:24. doi: 10.1186/s13018-014-0144-x.
- Background: PubMed 27125590Jabbari M, Hashempur MH, Razavi SZ, Shahraki HR, Kamalinejad M, Emtiazy M. Efficacy and short-term safety of topical Dwarf Elder (Sambucus ebulus L.) versus diclofenac for knee osteoarthritis: A randomized, double-blind, active-controlled trial. J Ethnopharmacol. 2016 Jul 21;188:80-6. doi: 10.1016/j.jep.2016.04.035. Epub 2016 Apr 26.
- Results publication: PubMed 18565256Fernandez-Lopez JC, Laffon A, Blanco FJ, Carmona L; EPISER Study Group. Prevalence, risk factors, and impact of knee pain suggesting osteoarthritis in Spain. Clin Exp Rheumatol. 2008 Mar-Apr;26(2):324-32.
- Individual participant dataSharing planned: Undecided
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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.
Moin Khan, MD principal investigator
MCMASTER
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Multiprofen in people with Knee Osteoarthritis, run by University of Michigan at 1 site in Canada.
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 4 inclusion and 5 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: stopped early, as of the sponsor's last update on 20 Mar 2019. 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 Canada. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated prematurely due to feasibility issues with rate of recruitment). Results are not available in the source record.
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?
Change in pain visual analog scale (VAS) scores (0-10) from baseline (time frame: week 0, week 3, week 6, week 12). 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 NCT03199417, which also lists 8 linked publications.
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 20 Mar 2019.