Osteoarthritis, KneeNCT03408145
Stem Cell and Growth Factor Injury and Arthritis Clinical Research Study
A study testing Hyaluronic Acid, Amniotic Tissue Allograft and Saline in people with Osteoarthritis, Knee, run by The Stone Research Foundation for Sports Medicine and Arthritis at 1 site in United States.
Trial summary
The investigators believe that amniotic tissue allografts may be an effective modality to treat osteoarthritis (OA) of the knee. One important mechanism of action may be stimulation of the synovial cells to increase production of endogenous hyaluronic acid (HA). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- Hyaluronic Acid, Amniotic Tissue Allograft and Saline
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jan 2018to 10 Oct 2020
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients age 18 and over
- Previous diagnosis of knee OA,
- Kellgren-Lawrence grade of 2 - 4
- Minimum Visual Analogue Scale (VAS) pain score of 3 on a scale of 0 - 10 where 0 is no pain and 10 is the highest level of pain
- Can give written informed consent
Who cannot join
- Receipt of HA, Platelet Rich Plasma (PRP) or amniotic cell injections in the previous 6 months
- Recent history of surgery to the same joint in the previous 3 months
- A clinical diagnosis of inflammatory arthritis made by history, examination or serology
- An active or latent infection of the affected knee joint or any other systemic infection currently under treatment or treated within the previous 3 months
- A history of chronic alcohol or drug abuse during the six months prior to the study
- Clinically documented acute or unstable concomitant disease, other than the condition to be treated in this study that might be a confounding reason for the presence of pathogens (i.e. renal, hepatic, cardiac, endocrine, hematologic, autoimmune, metabolic bone, crystal deposition, severe degenerative joint, neoplastic diseases)
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- Systemic or intra-articular administration, within twenty days prior to the procedure, of any type of corticosteroids, antineoplastic, immune stimulating or immunosuppressive agents
- Participation in any other investigational drug or device trial during the 30 days prior to screening visit or who will receive such a drug or device during the course of this study
- Pregnant females
- Subject is unable to understand verbal and/or written English
Trial locations and contacts
1 site in 1 country.
United States1 site
Stone Research Foundation
San Francisco, California, 94123
About this study
Official title: Short-Term Changes in Knee Synovial Fluid Composition Following Intraarticular Implantation of Amniotic Tissue Allograft
The investigators believe that amniotic tissue allografts may be an effective modality to treat osteoarthritis (OA) of the knee. One important mechanism of action may be stimulation of the synovial cells to increase production of endogenous hyaluronic acid (HA). A second mechanism may be the increase in the anabolic factors and a decrease in degenerative factors in the joint. The Investigators propose to quantify the concentration of HA and selected anabolic and degradative factors in synovial fluid aspirate pre and post implantation. While the treatment provided is designed to provide pain relief for symptoms, the purpose of this study is to learn more information about the impact of amniotic tissue allografts on inflammatory markers and growth factors in the knee joint.
Read the detailed description
The investigators believe that amniotic tissue allografts may be an effective modality to treat osteoarthritis (OA) of the knee. One important mechanism of action may be stimulation of the synovial cells to increase production of endogenous hyaluronic acid (HA). A second mechanism may be the increase in the anabolic factors and a decrease in degenerative factors in the joint. The Investigators propose to quantify the concentration of HA and selected anabolic and degradative factors in synovial fluid aspirate pre and post implantation. While the treatment provided is designed to provide pain relief for symptoms, the purpose of this study is to learn more information about the impact of amniotic tissue allografts on inflammatory markers and growth factors in the knee joint.
The purpose of this study is to determine the changes in the composition of synovial fluid resulting from implantation of amniotic tissue allograft in the knee.
This study will characterize the chemical profile of painful osteoarthritic joints and the influence of various injections containing cells and/or growth factors on that chemical profile. The addition of amniotic tissue allograft to HA injections may be an, effective treatment for people with knee pain resulting from OA and furthermore may lead to customization and/or the identification of the most efficacious combination of joint injections.
Prior to any study-related treatment, participants will undergo an Institutional Review Board (IRB)-approved informed consent process for aspiration of synovial fluid, followed by a randomized injection of either A) saline only, B) hyaluronic acid, C) amnionic allograft, or D) hyaluronic acid plus amnionic allograft, with a second aspiration performed 1 week after injection. Synovial fluid samples from 88 participants indicated for amniotic tissue implantation will be analyzed in vitro to determine the cellular and biochemical characterization of the fluid obtained.
The aim of this study is to determine the changes in composition of synovial fluid resulting from implantation of amniotic tissue allograft in the knee. There is always a possibility that the insertion of a needle may in itself result in a change in the composition of synovial fluid and therefore to increase the strength of the study control arm (placebo) is necessary. The placebo controlled group is justified to provide evidence that the standard of care and research treatments are safe and efficacious.
Participants will be randomly assigned to one of four treatment groups:
Group A: Placebo - saline Group B: Standard of care treatment - hyaluronic acid, Group C: Standard of care treatment - amnionic allograft, or Group D: Research treatment: hyaluronic acid plus amnionic allograft.
Prior to undergoing treatment, participants will be asked to complete a series of subjective health questionnaires. Upon completion of the questionnaires, a 1-2mL sample of synovial fluid will be aspirated from each subject. The collection of the synovial fluid is performed strictly for research purposes related to this study. Treatment will be administered according to the group the participant was randomly assigned to.
One week (+/- 3 days) following the treatment, the participant will return to the clinic, and will complete a second set of questionnaires, after which a second aspiration of 1-2mL of synovial fluid will be taken. If the participant received a placebo injection (saline only), they will be given an opportunity to receive an amniotic tissue allograft injection and/or hyaluronic acid .
Participation in this study will require that the investigators perform some procedures in addition to the standard of care. Standard of care is defined as:
- Receipt of a therapeutic injection of hyaluronic acid or implantation of amniotic tissue allograft
- Completion of subjective outcome questionnaires prior to treatment
Research specific procedures are defined as:
- Aspiration of knee synovial fluid during treatment
- Aspiration of knee synovial fluid one week after treatment
- Completion of subjective outcome questionnaires at one week following treatment
- Analysis of knee synovial fluid for increased levels of anabolic factors, IL1ra, TMP1, TMP2, HA, and IGF1 as well as decreased levels of degradative factors, IL-1, TNF-alpha, IL-10, MMP-2, MMP-9, TGF-beta
- Conditions
- Osteoarthritis, Knee
- Being tested
- Hyaluronic Acid, Amniotic Tissue Allograft, Saline
- Keywords
- Stem Cell Therapy, Injection, Hyaluronic Acid, Synovial Fluid
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyaluronic AcidDevice
Also called Viscosupplementation, Supartz
Injection of 3x 2.5ml of Hyaluronic Acid
Amniotic Tissue AllograftDevice
Also called Stem Cells, Growth Factors, Palingen InovoFLo
Injection of 1x 1ml of Amniotic Tissue Allograft
SalineDrug
Also called Sodium Chloride, NaCl
Injection of Saline
| Study group | Role | What they receive |
|---|---|---|
| Saline | Placebo comparator | The investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml and 1ml of Saline) comprising a total volume of 8.5ml fluid during one procedure. Receives: Drug: Saline |
| Hyaluronic Acid & Saline | Active comparator | The investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml of Hyaluronic Acid and 1ml Saline) comprising a total of 8.5mL fluid during one procedure. Receives: Device: Hyaluronic Acid; Drug: Saline |
| Amniotic Tissue & Saline | Active comparator | The investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml of Saline and 1ml Amniotic Tissue Allograft) comprising a total of 8.5mL fluid during one procedure. Receives: Device: Amniotic Tissue Allograft |
| Amniotic Tissue & Hyaluronic Acid | Experimental | The investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml of Hyaluronic Acid and 1ml Amniotic Tissue Allograft) comprising a total of 8.5mL fluid during one procedure. Receives: Device: Hyaluronic Acid; Device: Amniotic Tissue Allograft |
What is being measured
The primary outcome is the main question the study is designed to answer.
Knee Joint Chemical Profile
Evaluation of ELISA assay on synovial fluid aspirated pre and post study injection to ascertain the chemical profile of the joint for specific targets which include hyaluronic acid concentration, protein content and for increased levels of the following anabolic factors,IL1ra, TMP1, TMP2, HA, and IGF1 as well as decreased levels of the following degradative factors, IL-1, TNF-alpha, IL-10, MMP-2, MMP-9, TGF-beta5.
Measured: 1 week
Secondary outcomes (2)
VAS Pain scale
Measure self reported pain pre and post injection using Visual Analogue Scale rating 0 to 10, where 0 represents no pain and 10 represents worst imaginable pain.
Measured: 1 week
Function
Measure self reported function pre and post injections using the validated Knee Injury and Osteoarthritis Outcome Score (KOOS).
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2018
- Study start4 Jan 2018
- Primary completion10 Oct 2019
- Study completion10 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Stone Research Foundation for Sports Medicine and Arthritis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kevin R Stone, MD, Principal investigator, The Foundation for Sports Medicine and Arthritis Research (Stone Research Foundation)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03408145
- Sponsor's protocol ID
- SRF-037
- Status last verified
- Jun 2020
- First submitted
- 8 Jan 2018
- Last updated
- 25 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-Term Changes in Knee Synovial Fluid Composition Following Intraarticular Implantation of Amniotic Tissue Allograft
- ClinicalTrials.gov ID
- NCT03408145
- Acronym / sponsor ID
- SRF-037
- Conditions
- Osteoarthritis, Knee
- Keywords
- Stem Cell Therapy, Injection, Hyaluronic Acid, Synovial Fluid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- The Stone Research Foundation for Sports Medicine and ArthritisUniversity, hospital or other
- Study start
- 4 Jan 2018 (actual)
- Primary completion
- 10 Oct 2019 (actual)
- Study completion
- 10 Oct 2020 (actual)
- First posted
- 23 Jan 2018 (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.
The investigators believe that amniotic tissue allografts may be an effective modality to treat osteoarthritis (OA) of the knee. One important mechanism of action may be stimulation of the synovial cells to increase production of endogenous hyaluronic acid (HA). A second mechanism may be the increase in the anabolic factors and a decrease in degenerative factors in the joint. The Investigators propose to quantify the concentration of HA and selected anabolic and degradative factors in synovial fluid aspirate pre and post implantation. While the treatment provided is designed to provide pain relief for symptoms, the purpose of this study is to learn more information about the impact of amniotic tissue allografts on inflammatory markers and growth factors in the knee joint.
Detailed description
The investigators believe that amniotic tissue allografts may be an effective modality to treat osteoarthritis (OA) of the knee. One important mechanism of action may be stimulation of the synovial cells to increase production of endogenous hyaluronic acid (HA). A second mechanism may be the increase in the anabolic factors and a decrease in degenerative factors in the joint. The Investigators propose to quantify the concentration of HA and selected anabolic and degradative factors in synovial fluid aspirate pre and post implantation. While the treatment provided is designed to provide pain relief for symptoms, the purpose of this study is to learn more information about the impact of amniotic tissue allografts on inflammatory markers and growth factors in the knee joint.
The purpose of this study is to determine the changes in the composition of synovial fluid resulting from implantation of amniotic tissue allograft in the knee.
This study will characterize the chemical profile of painful osteoarthritic joints and the influence of various injections containing cells and/or growth factors on that chemical profile. The addition of amniotic tissue allograft to HA injections may be an, effective treatment for people with knee pain resulting from OA and furthermore may lead to customization and/or the identification of the most efficacious combination of joint injections.
Prior to any study-related treatment, participants will undergo an Institutional Review Board (IRB)-approved informed consent process for aspiration of synovial fluid, followed by a randomized injection of either A) saline only, B) hyaluronic acid, C) amnionic allograft, or D) hyaluronic acid plus amnionic allograft, with a second aspiration performed 1 week after injection. Synovial fluid samples from 88 participants indicated for amniotic tissue implantation will be analyzed in vitro to determine the cellular and biochemical characterization of the fluid obtained.
The aim of this study is to determine the changes in composition of synovial fluid resulting from implantation of amniotic tissue allograft in the knee. There is always a possibility that the insertion of a needle may in itself result in a change in the composition of synovial fluid and therefore to increase the strength of the study control arm (placebo) is necessary. The placebo controlled group is justified to provide evidence that the standard of care and research treatments are safe and efficacious.
Participants will be randomly assigned to one of four treatment groups:
Group A: Placebo - saline Group B: Standard of care treatment - hyaluronic acid, Group C: Standard of care treatment - amnionic allograft, or Group D: Research treatment: hyaluronic acid plus amnionic allograft.
Prior to undergoing treatment, participants will be asked to complete a series of subjective health questionnaires. Upon completion of the questionnaires, a 1-2mL sample of synovial fluid will be aspirated from each subject. The collection of the synovial fluid is performed strictly for research purposes related to this study. Treatment will be administered according to the group the participant was randomly assigned to.
One week (+/- 3 days) following the treatment, the participant will return to the clinic, and will complete a second set of questionnaires, after which a second aspiration of 1-2mL of synovial fluid will be taken. If the participant received a placebo injection (saline only), they will be given an opportunity to receive an amniotic tissue allograft injection and/or hyaluronic acid .
Participation in this study will require that the investigators perform some procedures in addition to the standard of care. Standard of care is defined as:
- Receipt of a therapeutic injection of hyaluronic acid or implantation of amniotic tissue allograft
- Completion of subjective outcome questionnaires prior to treatment
Research specific procedures are defined as:
- Aspiration of knee synovial fluid during treatment
- Aspiration of knee synovial fluid one week after treatment
- Completion of subjective outcome questionnaires at one week following treatment
- Analysis of knee synovial fluid for increased levels of anabolic factors, IL1ra, TMP1, TMP2, HA, and IGF1 as well as decreased levels of degradative factors, IL-1, TNF-alpha, IL-10, MMP-2, MMP-9, TGF-beta
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Saline | Placebo comparator | Drug: SalineThe investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml and 1ml of Saline) comprising a total volume of 8.5ml fluid during one procedure. |
| Hyaluronic Acid & Saline | Active comparator | Device: Hyaluronic Acid, Drug: SalineThe investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml of Hyaluronic Acid and 1ml Saline) comprising a total of 8.5mL fluid during one procedure. |
| Amniotic Tissue & Saline | Active comparator | Device: Amniotic Tissue AllograftThe investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml of Saline and 1ml Amniotic Tissue Allograft) comprising a total of 8.5mL fluid during one procedure. |
| Amniotic Tissue & Hyaluronic Acid | Experimental | Device: Hyaluronic Acid, Device: Amniotic Tissue AllograftThe investigators aspirate 1-2ml of Synovial Fluid from the knee joint prior to administering a series of four injections (2.5ml, 2.5ml, 2.5ml of Hyaluronic Acid and 1ml Amniotic Tissue Allograft) comprising a total of 8.5mL fluid during one procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients age 18 and over
- Previous diagnosis of knee OA,
- Kellgren-Lawrence grade of 2 - 4
- Minimum Visual Analogue Scale (VAS) pain score of 3 on a scale of 0 - 10 where 0 is no pain and 10 is the highest level of pain
- Can give written informed consent
Key exclusion criteria (10 listed)
- Receipt of HA, Platelet Rich Plasma (PRP) or amniotic cell injections in the previous 6 months
- Recent history of surgery to the same joint in the previous 3 months
- A clinical diagnosis of inflammatory arthritis made by history, examination or serology
- An active or latent infection of the affected knee joint or any other systemic infection currently under treatment or treated within the previous 3 months
- A history of chronic alcohol or drug abuse during the six months prior to the study
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 |
|---|---|---|
| Hyaluronic AcidAlso: Viscosupplementation, SupartzInjection of 3x 2.5ml of Hyaluronic Acid | Device | Amniotic Tissue & Hyaluronic Acid, Hyaluronic Acid & Saline |
| Amniotic Tissue AllograftAlso: Stem Cells, Growth Factors, Palingen InovoFLoInjection of 1x 1ml of Amniotic Tissue Allograft | Device | Amniotic Tissue & Hyaluronic Acid, Amniotic Tissue & Saline |
| SalineAlso: Sodium Chloride, NaClInjection of Saline | Drug | Hyaluronic Acid & Saline, Saline |
Primary outcome
Knee Joint Chemical Profile
Time frame: 1 week
Evaluation of ELISA assay on synovial fluid aspirated pre and post study injection to ascertain the chemical profile of the joint for specific targets which include hyaluronic acid concentration, protein content and for increased levels of the following anabolic factors,IL1ra, TMP1, TMP2, HA, and IGF1 as well as decreased levels of the following degradative factors, IL-1, TNF-alpha, IL-10, MMP-2, MMP-9, TGF-beta5.
2 secondary outcomes
VAS Pain scale
Time frame: 1 week
Function
Time frame: 1 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2021.
- Individual participant dataSharing planned: No
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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.
Kevin R Stone, MD principal investigator
The Foundation for Sports Medicine and Arthritis Research (Stone Research Foundation)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hyaluronic Acid, Amniotic Tissue Allograft and Saline in people with Osteoarthritis, Knee, run by The Stone Research Foundation for Sports Medicine and Arthritis at 1 site in United States.
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 5 inclusion and 10 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 25 Mar 2021. 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 United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Knee Joint Chemical Profile (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Mar 2021.