HemophiliaNCT02601170
Platelet-Rich Plasma Intra-Articular Injection in Treating Hemophilic Arthropathy
A study testing Platelet-Rich Plasma Intra-Articular Injection and Hyaluronic Acid Viscosupplementation in people with Hemophilia and Hemophilic Arthropathy, run by Tri-Service General Hospital (TSGH).
Trial summary
Severe hemophilia is characterized by frequent and lifelong bleeding, with more than 60% of bleeds occurring into joints . Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Hemophilia, Hemophilic Arthropathy
- What is being tested?
- Platelet-Rich Plasma Intra-Articular Injection and Hyaluronic Acid Viscosupplementation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- No sites listed yet
- Study dates
- Jun 2014to Jul 2016
- Phase
- Interventional
- 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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- hemophilia patients with hemophilic arthropathy of knee joints for at least 6 months
- painful (VAS ≥ 3) hemophilic arthropathy of knee joints after medication
Who cannot join
- presence of joint infections, any surgery on the joint in preceding 12 months
- intra-articular corticosteroid or HA injection within the past 6 months
- treatment with systemic steroids
- history of rheumatoid arthritis, or gouty arthropathy
- history of chicken or egg allergy
- presence of neoplasm
Show all 10Show fewer
- use of non steroidal anti-inflammatory drugs in the 5 days before study
- platelet values < 100,000/mm3
- acute hemarthrosis
- paresis, or recent trauma.
About this study
Severe hemophilia is characterized by frequent and lifelong bleeding, with more than 60% of bleeds occurring into joints . Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction. Currently available treatment of hemophilic arthropathy, such as analgesics, NSAIDs, and hyaluronic acid (HA), are predominantly directed toward the symptomatic relief of pain and inflammation, but they do little to reduce joint cartilage degeneration.
Platelet-Rich Plasma (PRP) is a simple and minimally invasive method that provides a natural concentrate of autologous growth factors from the blood. This method is now being increasingly applied in clinical practice to treat musculoskeletal disorders, such as tendon repairment and osteoarthritis. To the best of our knowledge, no study applies PRP for arthropathy of knee joint in hemophilia patients. The aim of the study is to investigate the efficacy, safety and duration of benefit of single PRP injection versus five weekly intra-articular injections of HA in patients with hemophilic arthropathy of knee.
Read the detailed description
Severe haemophilia is characterized by frequent and lifelong bleeding, with more than 60% of bleeds occurring into joints. Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction, which are associated with limitation of range of motion (ROM), pain, muscle atrophy, functional impairment, and poor quality of life. The knee, elbow, and ankle are the most commonly involved joints and arthropathy could worsen in adolescence or young adulthood. Hemophilic arthropathy is a multifactorial event and there is evidence to suggest that iron may play a major role with release of cytokines such as Interleukin ( IL)-1, IL-6, and tumour necrosis factor alpha (TNF-α) leading to chronic proliferative synovitis, hypervascularity, and progressive arthropathy. These effects on cartilage and subchondral bone are inflammatory and degenerative in nature and management of chronic hemophilic arthropathy is difficult.
Currently available drugs for the treatment of hemophilic arthropathy, such as analgesics, corticosteroids, nonsteroid and steroid anti-inflammatory drugs, and hyaluronic acid (HA), are predominantly directed toward the symptomatic relief of pain and inflammation, but they do little to reduce joint cartilage degeneration.
Platelet Rich Plasma (PRP) is a simple and minimally invasive method that provides a natural concentrate of autologous growth factors from the blood. This method is now being increasingly applied in clinical practice to treat musculoskeletal disorders, such as tendon repairment and osteoarthritis. Growth factors including platelet derived growth factor (PDGF), insulin growth factor (IGF), vascular endothelial growth factor, and transforming growth factor beta-1 are believed to be key components of PRP for structural repair. Although comparing PRP with other intra-articular and soft tissue injections has led to conflicting results, it seems that PRP has useful effects on healing and functional improvement of injured tissues. To the best of our knowledge, only one study applies PRP for arthropathy in haemophilia. Teyssler et al reported PRP could reduce pain of chronic ankle synovitis in hemophilia although the small sample size (n=6), short term follow-up and absence of a control group.
Hyaluronic acid (HA) has some role in joint mechanical support and its metabolic effects, which causes endogenous HA synthesis, stimulation of chondrocyte metabolism, synthesis of cartilage matrix components, and inhibition of chondrodegenerative enzymes, as well as inflammatory process. In 1994 Fernandez-Palazzi et al firstly used intra-articular HA injection for haemophiliacs with arthropathy and reported its beneficial effects in 2002. Recently, Carulli et al reported 27 haemophilic patients with a mean seven-year follow-up who had excellent results in terms of pain relief and functional improvement in the knee following treatment with HA injection. Viscosupplementation is a safe and effective therapeutic strategy in haemophilic arthropathy of knee in order to delay of surgery.
The aim of the study was to investigate the efficacy, safety and duration of benefit of single PRP injection versus five weekly intra-articular injections of HA in patients with haemophilic arthropathy of knee.
- Conditions
- Hemophilia, Hemophilic Arthropathy
- Being tested
- Platelet-Rich Plasma Intra-Articular Injection, Hyaluronic Acid Viscosupplementation
- Keywords
- Platelet Rich Plasma, Hemophilia, Hemophilic arthropathy
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Platelet-Rich Plasma Intra-Articular InjectionBiological
Hyaluronic Acid ViscosupplementationDrug
| Study group | Role | What they receive |
|---|---|---|
| PRP Group | Experimental | single intra-articular injection of 2mL PRP (RegentKit-THT-1, RegenLab SA, Mont-sur-Lausanne, Switzerland) Receives: Biological: Platelet-Rich Plasma Intra-Articular Injection |
| HA Group | Active comparator | five weekly intra-articular injections of 2.5 mL of hyaluronate sodium (ARTZDispo, Seikagaku Corporation Japan). Receives: Drug: Hyaluronic Acid Viscosupplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain (Visual Analogue Scale) and Change From Baseline at 1, 2, 3 &6 Months
The pain intensity will be evaluated subjectively on a visual analogue scale (0-10).
Higher scores mean a worse outcome.
Measured: baseline, 1 month, 2 months, 3 months, 6 months
Secondary outcomes (6)
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) From Baseline at 1, 2, 3 &6 Months
It consists of 24 items: five pertaining to pain perception, two to stiffness, and 17 to physical function.
Individual scores were then summed to form a raw score ranging from 0 (best) to 2400 (worst). Finally, WOMAC total score normalized between 0 (best) and 100 (worst).
Measured: baseline, 1 month, 2 months, 3 months, 6 months
Short Form-36 (SF-36) From Baseline at 1, 2, 3 &6 Months
The SF-36 is a 36-item assessment tool that measures eight general health concepts including physical functioning, role limitation due to physical health problems, bodily pain, general health, vitality, social functioning, role limitation due to emotional problems, and mental health. Individual scores were then summed to form a total score ranging from 0 (worst) to 100 (best). Higher scores mean a better outcome.
Measured: baseline, 1 month, 2 months, 3 months, 6 months
Ultrasonographic Synovial Thickness (mm) and Change From Baseline at 1, 2, 3 &6 Months
Synovial thickness (mm) by ultrasonography were evaluated from the lateral, middle, and medial aspects of the anterior suprapatellar recess
Measured: baseline, 1 month, 2 months, 3 months, 6 months
Synovial Hyperemia (Score) and Change From Baseline at 1, 2, 3 &6 Months
Power Doppler assessment of the selected synovial sites was performed with settings standardized to a pulse repetition frequency of 700 Hz. The power Doppler gain was adjusted to a level just below the disappearance of artifacts under the bony cortex.14,15 The intensity of blood flow in the synovium was scored on a semiquantitative scale from 0-3 (grade 0, no intraarticular colour signal; grade 1, up to 3 color signals or 2 single and 1 confluent signal in the intraarticular area; grade 2, greater than grade 1 to <50% of the intraarticular area filled with color signals; grade 3, ≥50% of the intraarticular area filled with color signals)
Measured: baseline, 1 month, 2 months, 3 months, 6 months
Range of Motion (ROM, Degrees) From Baseline at 1, 2, 3 &6 Months
Measured: baseline, 1 month, 2 months, 3 months, 6 months
Hemarthrosis From Baseline at 1, 2, 3 &6 Months
Episode(s) of hemarthrosis in the previous one month
Measured: baseline, 1 month, 2 months, 3 months, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2015 (estimated)
- Study startJun 2014
- Primary completionMay 2016
- Study completionJul 2016
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 HemophiliaStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tri-Service General Hospital (TSGH)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tsung-Ying Li, Tri-Service General Hospital (TSGH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02601170
- Sponsor's protocol ID
- 2-102-05-019
- Status last verified
- Aug 2020
- First submitted
- 7 Nov 2015
- Last updated
- 17 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet-Rich Plasma Intra-Articular Injection in Treating Hemophilic Arthropathy
- ClinicalTrials.gov ID
- NCT02601170
- Acronym / sponsor ID
- 2-102-05-019
- Conditions
- Hemophilia, Hemophilic Arthropathy
- Keywords
- Platelet Rich Plasma, Hemophilia, Hemophilic arthropathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Tri-Service General Hospital (TSGH)University, hospital or other
- Study start
- Jun 2014
- Primary completion
- May 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 10 Nov 2015 (estimated)
- Results
- Posted 17 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Severe hemophilia is characterized by frequent and lifelong bleeding, with more than 60% of bleeds occurring into joints . Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction. Currently available treatment of hemophilic arthropathy, such as analgesics, NSAIDs, and hyaluronic acid (HA), are predominantly directed toward the symptomatic relief of pain and inflammation, but they do little to reduce joint cartilage degeneration.
Platelet-Rich Plasma (PRP) is a simple and minimally invasive method that provides a natural concentrate of autologous growth factors from the blood. This method is now being increasingly applied in clinical practice to treat musculoskeletal disorders, such as tendon repairment and osteoarthritis. To the best of our knowledge, no study applies PRP for arthropathy of knee joint in hemophilia patients. The aim of the study is to investigate the efficacy, safety and duration of benefit of single PRP injection versus five weekly intra-articular injections of HA in patients with hemophilic arthropathy of knee.
Detailed description
Severe haemophilia is characterized by frequent and lifelong bleeding, with more than 60% of bleeds occurring into joints. Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction, which are associated with limitation of range of motion (ROM), pain, muscle atrophy, functional impairment, and poor quality of life. The knee, elbow, and ankle are the most commonly involved joints and arthropathy could worsen in adolescence or young adulthood. Hemophilic arthropathy is a multifactorial event and there is evidence to suggest that iron may play a major role with release of cytokines such as Interleukin ( IL)-1, IL-6, and tumour necrosis factor alpha (TNF-α) leading to chronic proliferative synovitis, hypervascularity, and progressive arthropathy. These effects on cartilage and subchondral bone are inflammatory and degenerative in nature and management of chronic hemophilic arthropathy is difficult.
Currently available drugs for the treatment of hemophilic arthropathy, such as analgesics, corticosteroids, nonsteroid and steroid anti-inflammatory drugs, and hyaluronic acid (HA), are predominantly directed toward the symptomatic relief of pain and inflammation, but they do little to reduce joint cartilage degeneration.
Platelet Rich Plasma (PRP) is a simple and minimally invasive method that provides a natural concentrate of autologous growth factors from the blood. This method is now being increasingly applied in clinical practice to treat musculoskeletal disorders, such as tendon repairment and osteoarthritis. Growth factors including platelet derived growth factor (PDGF), insulin growth factor (IGF), vascular endothelial growth factor, and transforming growth factor beta-1 are believed to be key components of PRP for structural repair. Although comparing PRP with other intra-articular and soft tissue injections has led to conflicting results, it seems that PRP has useful effects on healing and functional improvement of injured tissues. To the best of our knowledge, only one study applies PRP for arthropathy in haemophilia. Teyssler et al reported PRP could reduce pain of chronic ankle synovitis in hemophilia although the small sample size (n=6), short term follow-up and absence of a control group.
Hyaluronic acid (HA) has some role in joint mechanical support and its metabolic effects, which causes endogenous HA synthesis, stimulation of chondrocyte metabolism, synthesis of cartilage matrix components, and inhibition of chondrodegenerative enzymes, as well as inflammatory process. In 1994 Fernandez-Palazzi et al firstly used intra-articular HA injection for haemophiliacs with arthropathy and reported its beneficial effects in 2002. Recently, Carulli et al reported 27 haemophilic patients with a mean seven-year follow-up who had excellent results in terms of pain relief and functional improvement in the knee following treatment with HA injection. Viscosupplementation is a safe and effective therapeutic strategy in haemophilic arthropathy of knee in order to delay of surgery.
The aim of the study was to investigate the efficacy, safety and duration of benefit of single PRP injection versus five weekly intra-articular injections of HA in patients with haemophilic arthropathy of knee.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PRP Group | Experimental | Biological: Platelet-Rich Plasma Intra-Articular Injectionsingle intra-articular injection of 2mL PRP (RegentKit-THT-1, RegenLab SA, Mont-sur-Lausanne, Switzerland) |
| HA Group | Active comparator | Drug: Hyaluronic Acid Viscosupplementationfive weekly intra-articular injections of 2.5 mL of hyaluronate sodium (ARTZDispo, Seikagaku Corporation Japan). |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- hemophilia patients with hemophilic arthropathy of knee joints for at least 6 months
- painful (VAS ≥ 3) hemophilic arthropathy of knee joints after medication
Key exclusion criteria (10 listed)
- presence of joint infections, any surgery on the joint in preceding 12 months
- intra-articular corticosteroid or HA injection within the past 6 months
- treatment with systemic steroids
- history of rheumatoid arthritis, or gouty arthropathy
- history of chicken or egg allergy
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 |
|---|---|---|
| Platelet-Rich Plasma Intra-Articular Injection | Biological | PRP Group |
| Hyaluronic Acid Viscosupplementation | Drug | HA Group |
Primary outcome
Pain (Visual Analogue Scale) and Change From Baseline at 1, 2, 3 &6 Months
Time frame: baseline, 1 month, 2 months, 3 months, 6 months
The pain intensity will be evaluated subjectively on a visual analogue scale (0-10). Higher scores mean a worse outcome.
6 secondary outcomes
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) From Baseline at 1, 2, 3 &6 Months
Time frame: baseline, 1 month, 2 months, 3 months, 6 months
Short Form-36 (SF-36) From Baseline at 1, 2, 3 &6 Months
Time frame: baseline, 1 month, 2 months, 3 months, 6 months
Ultrasonographic Synovial Thickness (mm) and Change From Baseline at 1, 2, 3 &6 Months
Time frame: baseline, 1 month, 2 months, 3 months, 6 months
Synovial Hyperemia (Score) and Change From Baseline at 1, 2, 3 &6 Months
Time frame: baseline, 1 month, 2 months, 3 months, 6 months
Range of Motion (ROM, Degrees) From Baseline at 1, 2, 3 &6 Months
Time frame: baseline, 1 month, 2 months, 3 months, 6 months
Hemarthrosis From Baseline at 1, 2, 3 &6 Months
Time frame: baseline, 1 month, 2 months, 3 months, 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Platelet-Rich Plasma Intra-Articular Injection and Hyaluronic Acid Viscosupplementation in people with Hemophilia and Hemophilic Arthropathy, run by Tri-Service General Hospital (TSGH).
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 2 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 17 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Yes. Results are posted in the registry (first posted 17 Sep 2020). 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?
Pain (Visual Analogue Scale) and Change From Baseline at 1, 2, 3 &6 Months (time frame: baseline, 1 month, 2 months, 3 months, 6 months). 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 17 Sep 2020.