IL-1RA Treatment in Patients With Acute ACL Tear and Painful Effusions
| Status: | Not yet recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 14 - 33 |
| Updated: | 8/29/2018 |
| Start Date: | September 1, 2018 |
| End Date: | December 31, 2021 |
| Contact: | Caitlin Conley, PhD |
| Email: | caitlin.whale@uky.edu |
| Phone: | 859-257-1939 |
A Prospective, Single-Center, Randomized, Triple-Blinded, Placebo-Controlled Study of IL-1RA Treatment in Patients With Acute ACL Tear and Painful Effusions
Injury to the knee during sports participation often involves partial or full detachment of
the anterior cruciate ligament (abbreviated as ACL). ACL tears cause pain, swelling and
inflammation. While the swelling and inflammation usually goes away in time, individuals with
ACL injuries may experience pain and notice knee instability (knee slipping, etc.). Often
surgery can repair or replace the ACL within the joint, allowing individuals the ability to
walk or run again pain free or participate in sports. Unfortunately, osteoarthritis of the
knee, which also causes pain and swelling, can occur in that same knee 10-20 years later for
reasons which are not well understood.
In this research study, the investigator hopes to reduce the initial pre-operative pain. The
reduction of pain will allow for earlier movement of the knee joint and preparation for
surgery. The investigator is interested to see if the use of Kineret does decrease the risk
of developing arthritis in individuals with ACL injuries by treating them within 1-7 days
after their injury.
the anterior cruciate ligament (abbreviated as ACL). ACL tears cause pain, swelling and
inflammation. While the swelling and inflammation usually goes away in time, individuals with
ACL injuries may experience pain and notice knee instability (knee slipping, etc.). Often
surgery can repair or replace the ACL within the joint, allowing individuals the ability to
walk or run again pain free or participate in sports. Unfortunately, osteoarthritis of the
knee, which also causes pain and swelling, can occur in that same knee 10-20 years later for
reasons which are not well understood.
In this research study, the investigator hopes to reduce the initial pre-operative pain. The
reduction of pain will allow for earlier movement of the knee joint and preparation for
surgery. The investigator is interested to see if the use of Kineret does decrease the risk
of developing arthritis in individuals with ACL injuries by treating them within 1-7 days
after their injury.
Kineret® was chosen because it is safe, well tolerated, and has been used to treat Rheumatoid
Arthritis (RA) and post-surgical persistent knee effusions as well as knee stiffness.
Although Kineret® is approved by the US Food and Drug Administration (FDA) for the treatment
of RA and Neonatal-Onset Multisystem Inflammatory Disease, it is not currently approved by
the FDA for use in treating ACL injury. Therefore, the use of Kineret® in this study is
investigational.
The research procedures will be conducted at the University of Kentucky (UK) Medical Center.
Participants will need to come to the UK Healthcare at Turfland located at 2195 Harrodsburg
Road in Lexington, KY. Participants will be asked to come to this location seven times during
the study. Each of those visits will take about 30 minutes. All exams and questionnaires will
be administered during the otherwise necessary routine visits for any participant who has
suffered an ACL tear. No additional visit is necessary. The total amount of time commitment
for participation in this study is about 6 1/2 hours, over the next 2 years.
All participants with sports related ACL injuries enrolled in this study will be seen and may
elect to undergo surgery, if necessary. Note: Surgery is not part of this protocol. Should
participants be enrolled into the study and choose not to undergo ACL reconstruction
(surgery), they will receive treatment according to this protocol.
Randomization: Once it has been determined that a participant qualifies for entry into the
study, they will be randomized, like the flipping of coin into one of three treatment groups.
All groups will receive knee injections with either Kineret® or a saline placebo. The saline
placebo will contain no active medication. Both the participant and study doctor will be no
know what treatment group the participant is assigned to. However, in case of an emergency,
the investigator will be able to find out what treatment group the participant has been
assigned to.
- Group 1: A saline placebo injection at Visit 1 and Kineret® 150mg at Visit 2.
- Group 2: Kineret®, 150mg at Visit 1 and saline placebo at Visit 2.
- Group 3: Saline placebo at Visits 1 and 2.
X-rays: All participants would have undergone a routine clinical x-ray analysis at prior to
Visit 1.
MRI: All participants will undergo initial MRI examination to confirm ACL injury at Visit 1
and subsequent MRIs will be performed at Visits 6 and 7.
Participants will undergo knee aspirations. During a knee aspiration, the investigator will
remove fluid from the space around the knee using a needle and syringe. This is usually
performed under a local anesthetic to either relieve swelling or to obtain fluid for analysis
to diagnose a joint disorder and/or problem. Knee aspirations after ACL tear with a painful
effusion are a common orthopaedic practice and standard of care in at the UK Medical Center.
Thus they are not considered additional interventions with regard to this study unless the
participant has no fluid in the knee.
At Visit 1: Participants may have a large effusion that requires aspiration. This would be
done as part of the participants normal routine care.
At Visit 2: Participants may have to undergo a study required aspiration depending on the
amount of fluid in the knee. This will be performed for the purpose of the research.
At Visit 3: Should the participant elect to undergo ACL reconstruction surgery, they will
undergo a study required knee aspiration. This will be performed for the purpose of the
research.
At Visit 4: Should the participant elect to undergo ACL reconstruction surgery, and there is
substantial post-operative fluid in the knee, the investigator may choose to aspirate the
knee again. This would be done as part of the participants normal routine care.
After the aspiration procedure: Once home, it is important for the participant to keep the
joint aspiration site clean and dry. The aspiration site may be tender or sore for a few days
after the joint aspiration procedure. The investigator will instruct the participant on what
pain reliever they may take.
Below is breakdown of what will happen at each study visit:
Visit 1 Screening (1-7 days following injury)
- Obtain informed consent and assent if necessary
- Medical history reviewed for inclusion/exclusion criteria
- Medications history reviewed for inclusion/exclusion
- Medical examinations and collect vital signs .All participants must have a clinical exam
that is consistent with an ACL tear.
- Collection of urine and blood for laboratory testing. Women of child bearing potential
will be given a urine pregnancy test. Test must be negative in order to enroll into the
study.
- Participant will have the following assessments: range of motion, knee instability
(Lachman's test) and standardized MTP-2 weight bearing x-rays and be asked to fill out
several questionnaires.
- Pre-Surgery MRI
Once eligibility is determined, participants will be randomized into 1 or 3 treatment groups.
Following randomizing, participants will undergo a knee aspiration and will receive their
first dose study medication.
Visit 2 (10-17 days post injury):
- Knee aspiration
- Study medication injection
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (urine, blood)
Visit 3 (day of surgery or 4-6 weeks post injury)
- Knee aspiration (in the operating room under anesthesia)
- Patient reported outcomes (PROs) administered prior to surgery
- Pain Questionnaires administered prior to surgery
- Biomarkers (urine and blood)
Visit 4 (2 weeks post injury)
- Knee aspiration (if clinically indicated)
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (urine and blood)
Visit 5 (6 month post-op)
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
Visit 6 (12 months post op)
- MRI
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (serum and urine only)
Visit 7 (24 month post-up)
- MRI
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (serum and urine only)
The blood and fluid samples collected from the participants will NOT UNDERGO GENETIC TESTING.
Samples will be analyzed and stored at a UK research laboratory. The will be tested for
special markers of cartilage breakdown and will remain property of the University of Kentucky
indefinitely or until they are completely used. The results from the analyzed samples are
important only for research For this reason, these results will not be released to either the
participant or their family.
Either the participant or their insurance company, Medicare or Medicaid will be responsible
for the costs of all care and treatment they receive during this study that they would
normally receive for their condition.
The University of Kentucky may not be allowed to bill an insurance company, Medicare or
Medicaid for the medical procedures done strictly for research. These costs include the
following:
- X-ray of the knee done at Visit 1
- Knee aspiration done at Visit 1 and Visit 4 (if necessary)
The University of Kentucky may not be allowed to bill your insurance company, Medicare or
Medicaid for the medical procedures done strictly for research. The following will be
provided at no cost to you: the injection of Kineret®, the second knee aspiration and
potentially the third knee aspiration, questionnaires and three MRIs.
Participants will receive $150.00 for taking part in this study. They will receive $50.00 for
each MRI completed. Payment will be in the form of a check which will be mailed approximately
four to six weeks following the study visit. If the participant is a child the compensation
will be mailed to the child.
Should a participant decide to withdraw from the study early they will be compensated for
their time and travel.
Arthritis (RA) and post-surgical persistent knee effusions as well as knee stiffness.
Although Kineret® is approved by the US Food and Drug Administration (FDA) for the treatment
of RA and Neonatal-Onset Multisystem Inflammatory Disease, it is not currently approved by
the FDA for use in treating ACL injury. Therefore, the use of Kineret® in this study is
investigational.
The research procedures will be conducted at the University of Kentucky (UK) Medical Center.
Participants will need to come to the UK Healthcare at Turfland located at 2195 Harrodsburg
Road in Lexington, KY. Participants will be asked to come to this location seven times during
the study. Each of those visits will take about 30 minutes. All exams and questionnaires will
be administered during the otherwise necessary routine visits for any participant who has
suffered an ACL tear. No additional visit is necessary. The total amount of time commitment
for participation in this study is about 6 1/2 hours, over the next 2 years.
All participants with sports related ACL injuries enrolled in this study will be seen and may
elect to undergo surgery, if necessary. Note: Surgery is not part of this protocol. Should
participants be enrolled into the study and choose not to undergo ACL reconstruction
(surgery), they will receive treatment according to this protocol.
Randomization: Once it has been determined that a participant qualifies for entry into the
study, they will be randomized, like the flipping of coin into one of three treatment groups.
All groups will receive knee injections with either Kineret® or a saline placebo. The saline
placebo will contain no active medication. Both the participant and study doctor will be no
know what treatment group the participant is assigned to. However, in case of an emergency,
the investigator will be able to find out what treatment group the participant has been
assigned to.
- Group 1: A saline placebo injection at Visit 1 and Kineret® 150mg at Visit 2.
- Group 2: Kineret®, 150mg at Visit 1 and saline placebo at Visit 2.
- Group 3: Saline placebo at Visits 1 and 2.
X-rays: All participants would have undergone a routine clinical x-ray analysis at prior to
Visit 1.
MRI: All participants will undergo initial MRI examination to confirm ACL injury at Visit 1
and subsequent MRIs will be performed at Visits 6 and 7.
Participants will undergo knee aspirations. During a knee aspiration, the investigator will
remove fluid from the space around the knee using a needle and syringe. This is usually
performed under a local anesthetic to either relieve swelling or to obtain fluid for analysis
to diagnose a joint disorder and/or problem. Knee aspirations after ACL tear with a painful
effusion are a common orthopaedic practice and standard of care in at the UK Medical Center.
Thus they are not considered additional interventions with regard to this study unless the
participant has no fluid in the knee.
At Visit 1: Participants may have a large effusion that requires aspiration. This would be
done as part of the participants normal routine care.
At Visit 2: Participants may have to undergo a study required aspiration depending on the
amount of fluid in the knee. This will be performed for the purpose of the research.
At Visit 3: Should the participant elect to undergo ACL reconstruction surgery, they will
undergo a study required knee aspiration. This will be performed for the purpose of the
research.
At Visit 4: Should the participant elect to undergo ACL reconstruction surgery, and there is
substantial post-operative fluid in the knee, the investigator may choose to aspirate the
knee again. This would be done as part of the participants normal routine care.
After the aspiration procedure: Once home, it is important for the participant to keep the
joint aspiration site clean and dry. The aspiration site may be tender or sore for a few days
after the joint aspiration procedure. The investigator will instruct the participant on what
pain reliever they may take.
Below is breakdown of what will happen at each study visit:
Visit 1 Screening (1-7 days following injury)
- Obtain informed consent and assent if necessary
- Medical history reviewed for inclusion/exclusion criteria
- Medications history reviewed for inclusion/exclusion
- Medical examinations and collect vital signs .All participants must have a clinical exam
that is consistent with an ACL tear.
- Collection of urine and blood for laboratory testing. Women of child bearing potential
will be given a urine pregnancy test. Test must be negative in order to enroll into the
study.
- Participant will have the following assessments: range of motion, knee instability
(Lachman's test) and standardized MTP-2 weight bearing x-rays and be asked to fill out
several questionnaires.
- Pre-Surgery MRI
Once eligibility is determined, participants will be randomized into 1 or 3 treatment groups.
Following randomizing, participants will undergo a knee aspiration and will receive their
first dose study medication.
Visit 2 (10-17 days post injury):
- Knee aspiration
- Study medication injection
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (urine, blood)
Visit 3 (day of surgery or 4-6 weeks post injury)
- Knee aspiration (in the operating room under anesthesia)
- Patient reported outcomes (PROs) administered prior to surgery
- Pain Questionnaires administered prior to surgery
- Biomarkers (urine and blood)
Visit 4 (2 weeks post injury)
- Knee aspiration (if clinically indicated)
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (urine and blood)
Visit 5 (6 month post-op)
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
Visit 6 (12 months post op)
- MRI
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (serum and urine only)
Visit 7 (24 month post-up)
- MRI
- Patient reported outcomes (PROs) administered
- Pain Questionnaires administered
- Biomarkers (serum and urine only)
The blood and fluid samples collected from the participants will NOT UNDERGO GENETIC TESTING.
Samples will be analyzed and stored at a UK research laboratory. The will be tested for
special markers of cartilage breakdown and will remain property of the University of Kentucky
indefinitely or until they are completely used. The results from the analyzed samples are
important only for research For this reason, these results will not be released to either the
participant or their family.
Either the participant or their insurance company, Medicare or Medicaid will be responsible
for the costs of all care and treatment they receive during this study that they would
normally receive for their condition.
The University of Kentucky may not be allowed to bill an insurance company, Medicare or
Medicaid for the medical procedures done strictly for research. These costs include the
following:
- X-ray of the knee done at Visit 1
- Knee aspiration done at Visit 1 and Visit 4 (if necessary)
The University of Kentucky may not be allowed to bill your insurance company, Medicare or
Medicaid for the medical procedures done strictly for research. The following will be
provided at no cost to you: the injection of Kineret®, the second knee aspiration and
potentially the third knee aspiration, questionnaires and three MRIs.
Participants will receive $150.00 for taking part in this study. They will receive $50.00 for
each MRI completed. Payment will be in the form of a check which will be mailed approximately
four to six weeks following the study visit. If the participant is a child the compensation
will be mailed to the child.
Should a participant decide to withdraw from the study early they will be compensated for
their time and travel.
Inclusion Criteria:
- Acute ACL Tear and Painful Effusions
- Signed and dated combined informed consent/HIPAA form and if a minor, a signed assent.
- Willingness to comply with all study procedures and availability for the duration of
the study
- For females of reproductive potential: use of highly effective contraception.
- Currently participating in a sporting activity
- Documentation of closed growth plates as noted on the screening x-ray
Exclusion Criteria:
- underlying inflammatory disease (i.e. Rheumatoid Arthritis, Psoriatic Arthritis etc)
- have been diagnosed with hepatitis B or tuberculosis
- currently have an infections, including infection of the skin, or have signs and
symptoms of an infection, including fever.
- any abnormalities in their white blood cell counts
- have a disease that weakens your immune system such as diabetes, cancer, HIV or AIDs
- other major medical condition requiring treatment with immunosuppressant or modulating
drugs.
- A history of chronic use of non-steroidal anti-inflammatory drugs
- Currently taking immunosuppressant medication, including oral and parenteral
corticosteroids (topical and stable dose inhaled corticosteriods are acceptable)
- Females who are pregnant or breastfeeding
- Received a "live" vaccine (smallpox, MMR (measles, mumps and rubella), flu, polio,
typhoid, chicken pox, yellow fever, herpes zoster) 4 weeks prior to screening.
- A history of bleeding disorders or are taking any blood thinning medications, aspirin
or other medications affecting blood clotting.
- Previous exposure or allergic reaction to anakinra
- Allergy to latex or tape
- Allergy to Kineret or have had a reaction to any local or general anesthesia
- prior knee surgery (Ipsilateral or contralateral)
- have received any investigational drug with 4 weeks of study Visit 1
We found this trial at
1
site
2195 Harrodsburg Road
Lexington, Kentucky 40504
Lexington, Kentucky 40504
Principal Investigator: Christian Lattermann, MD
Phone: 859-218-0839
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