Effectiveness of Stromal Vascular Fraction (SVF) and Platelets Rich Plasma (PRP) in Osteoarthritis and Tendinopathy (SPOT)

December 14, 2022 updated by: Adrien Schwitzguebel

Effectiveness of Stromal Vascular Fraction (SVF) and Platelets Rich Plasma (PRP) in Osteoarthritis and Tendinopathy: Study Protocol for a Phase III, Prospective, Randomized, Controlled Multi-center Study: (SPOT Study).

In a multi-centric, randomized, triple-blind controlled trial, 195 patients will be separated in 2 subgroups: 130 individuals with osteoarthritis and 65 with tendinopathies. The mian question to answer are the effect of SVF on :

  • The clinical improvenent
  • The cartilage thickness evolution in case of osteoarthritis
  • The tendon healing in case of thendinopathy

Patients will receive an initial single PRP or PRP + SVF injection followed by one- and two-months PRP doses. In parallel, they will beneficiate of a proper rehabilitation plan with active physical therapies.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

Osteoarthritis and tendinopathies are two frequent diseases with a high social and individual impact. Both have multifactorial etiology and the development of therapeutic options is a public health priority. Osteoarthritis is the most common joint disease, and more than 30% of sports-related injuries have a component of tendinopathy.

Most common conservative treatments for osteoarthritis treatment include painkillers, active physical therapies, orthotics, infiltrations of corticosteroids, hyaluronic acid (HA), and platelet-rich plasma (PRP).

PRP may be beneficial in both tendinopathy and osteoarthritis by interfering with catabolic and inflammatory events and by subsequently promoting anabolic responses. Activation of PRP releases biologically active components, including platelet-derived growth factor (PDGF), transforming growth factor-β (PGF-β), type I insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF). These proteins are responsible for a range of critical tissue healing roles such as chondrocyte and mesenchymal stem cells proliferation, bone and vessel remodeling, inflammatory modulation and collagen synthesis.

For osteoarthritis, an improvement of clinical outcomes is clearly established, presumably associated with the chondroprotective effect of PRP. Nevertheless, an in-vivo effect on human cartilage regeneration is not yet demonstrated despite the numerous studies approaching the subject.

Most common conservative treatments for tendinopathies include painkillers, bracing, active physical therapies, extracorporeal shockwave therapy, other specific therapies (cryotherapy, red light therapy, topical glycerol trinitrate, PRP and tendon lengthening. Clear clinical benefits are currently demonstrated with active exercises and extracorporeal shockwave therapies. Tendon needling, also known as tendon fenestration or percutaneous needle tenotomy, intends to disrupt the chronic inflammatory and degenerative processes through localized bleeding, fibroblastic proliferation, and organized collagen synthesis. The intervened tendon can also lengthen in some cases.

Preclinical models elucidated how injected Adipose Derived- Mesenchymal Stem Cells (AD-MSC) coordinate the cartilage regeneration process through paracrine mechanisms, producing cytokines and trophic bioactive factors that stimulate cellular proliferation, reduce inflammation, fibrosis, oxidative stress, and chondrocytes senescence.

Stromal Vascular Fraction (SVF), a product from specific adipose tissue processing, contains mesenchymal stem cells, endothelial precursor cells, T regulatory cells, macrophages, smooth muscle cells, pericytes and preadipocytes. SVF extraction and injection techniques have been recently used as an alternative to harvest AD-MSC due to its logistic simplicity and feasibility in clinical practice.

SVF injections produce a clinically significant effect on the treatment of knee osteoarthritis, and a possible improvement in cartilage quality. Promising results were observed in the Achilles tendon.

This clinical trial aims to assess the clinical efficacy of SVF as adjuvant therapy to PRP on functionality and tissue regeneration on osteoarthritis and tendinopathies.

Study Type

Interventional

Enrollment (Anticipated)

195

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Informed Consent as documented by signature (Appendix Informed Consent Form)
  • Age older than 16 years old,
  • Symptomatic osteoarthritis of the hip, knee, ankle, elbow, shoulder confirmed by MRI or symptomatic tendinopathy confirmed by ultrasonography,
  • Failure of first-line conservative management in the last 3 months including medical or infiltrative treatment, orthotics use, active rehabilitation plan, adaptation of sports and work habits.

Exclusion Criteria:

  • Patient is familiar with the lipoaspiration process
  • In case of tendinopathy: significant impingement according to investigator's judgement
  • Subacromial impingement of the supraspinatus tendon, Haglund disease with erosion of the anterior part of Achilles tendon
  • Significant disease of the contralateral member with a function evaluated with SANE score below 80%
  • In case of osteoarthritis: microcristalline disease (i.e. gout, pseudogout),
  • Active inflammatory rheumatic disorders,
  • Need of regular anti-inflammatory treatment (either NSAIDs or corticosteroids),
  • Allergy to local anesthetics or epinephrin
  • Bleeding disorders or current anticoagulation therapy
  • Patients with decompensated renal failure, hepatic dysfunction, or severe pulmonary or cardiovascular disease,
  • Patients with an immunocompromised status
  • Women who are pregnant or intend to become pregnant during the study
  • Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant,
  • Known or suspected non-compliance, drug, or alcohol abuse
  • Previous enrollment into the current study,
  • Participation in another study with investigational drug or procedure within the 30 days preceding and during the present study
  • Enrollment of the investigator, his/her family members, employees, and other dependent persons

If a bilateral disease is present and both sides require either the experimental or the control intervention, only the most symptomatic side will be studied.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SVF (Stromal vascular fraction)

Patients will receive a venepuncture to obtain PRP, and a lipoaspirate to obtain SVF. Then an ultrasonographic guided PRP+SVF injection will be performed.

Patients will consecutively receive two monthly PRP injections. Patients in tendinopathies subgroup will besides undergo tendon needling concomitant to each injecetion.
Device: Stromal Vascular Fraction infiltration
Procedure to prepare SVF: In the operations room and after aseptic technic, local anesthesia is applied in the liposuction incision site with lidocaine 1% without epinephrine subcutaneously. 60 ml of tumescent solution are injected. After 15-20 minutes waiting, 15 ml of lipoaspiration per side are recollected into a double syringe. This is centrifuged for 4 minutes at 2.500 rpm and the remaining fat is separated from the other fractions. Two 1.4 mm GEMS syringes are attached together, and fat is transferred at least 30 times from one syringe to the other. Syringe content is again centrifugated for 4 minutes. The oil is discarded and approximately 1.5ml SVF fraction remains.
Other Names:
  • Autologous conditionned adipose tissue (ACA) kit by Arthrex
Active Comparator: PRP (Platelet-rich plasma)

Patients will receive a venepuncture to obtain PRP, and a sham lipoaspirate. Then an ultrasonographic guided PRP injection will be performed.

Patients will consecutively receive two monthly PRP injections. Patients in tendinopathies subgroup will besides undergo tendon needling concomitant to each injecetion.
Procedure: Plattelet Rich Plasma infiltration
Procedure to prepare PRP: 15 cm of peripheral blood obtained by venipuncture are centrifugated at 5000 RPM during 5 minutes. Using PRP Arthrex kit platelets poor plasma is discarded and 1-3 mm of PRP are ready to be injected
Other Names:
  • Autologous conditionned plasma (ACP) kit by Arthrex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SANE
Time Frame: 6 months
The absolute difference (changes from baseline to other time points) between the treatment and control groups on the Single Assessment Numeric Evaluation (0 meaning the poorest function to 100 meaning an optimal function).
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quick DASH
Time Frame: 1, 2, 3, 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control groups on the Quick Disabilities of Arm, Shoulder, and Hand score for the superior member (0 meaning lower disability to 100 meaning most severe disability).
1, 2, 3, 6, and 12 months
LEFS
Time Frame: 1, 2, 3, 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on the Low Extremity Functional Scale for the inferior member (0 meaning lower disability to 80 meaning most severe disability).
1, 2, 3, 6, and 12 months
VAS
Time Frame: 1, 2, 3, 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on the Visual Analogue Scale (VAS) on a 0 to 10 scale. 0: no pain, 10: maximal pain
1, 2, 3, 6, and 12 months
SANE
Time Frame: 1, 2, 3, 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on the Single Assessment Numeric Evaluation (SANE). From 0% functional to 100% being normal function.
1, 2, 3, 6, and 12 months
WOMAC
Time Frame: 1, 2, 3, 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on the Western Ontario McMaster Universities Osteoarthritis Index on knee osteoarthritis cases. From 0 to 96, being 0: no limitation, 96: extreme limitation
1, 2, 3, 6, and 12 months
Return to work
Time Frame: 1, 2, 3, 6, and 12 months
The absolute difference between the treatment and control arms on Return to work in days since treatment
1, 2, 3, 6, and 12 months
Return to sport
Time Frame: 1, 2, 3, 6, and 12 months
The absolute difference between the treatment and control arms on the Return to sport in days since treatment
1, 2, 3, 6, and 12 months
cross-sectional tendon surface
Time Frame: 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on the Affected cross-sectional tendon surface in mm2 on ultrasound
6, and 12 months
Tendon quality with elastography
Time Frame: 6 and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on Affected tendon quality with elastography (difference in kilopascals from the healthy side) on ultrasound
6 and 12 months
Doppler enhancement
Time Frame: 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on Ultrasonographic doppler reaction judged as "absent", "minimal", "less than 1/3 of the affected area", "1/3-2/3 of the affected area" or "more than 2/3 of the affected area".
6, and 12 months
tendon tear size evolution
Time Frame: 2, 3, 6, and 12 months
The absolute difference (changes from baseline to other time points) between the treatment and control arms on tendon tear size evolution from baseline in mm3
2, 3, 6, and 12 months
AMADEUS SCORE
Time Frame: 6 and 12 moths
The absolute difference (changes from baseline to other time points) between the treatment and control arms on Affected cartilage quality on MRI using Area Measurement And Depth Underlying Structures (AMADEUS) score. (0 worst, 100 best)
6 and 12 moths

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Age
Time Frame: Baseline
Age
Baseline
BMI
Time Frame: Baseline
BMI
Baseline
Sex
Time Frame: Baseline
Sex
Baseline
Height
Time Frame: Baseline
Height, cm
Baseline
Weight
Time Frame: Baseline
Weight, kg
Baseline
Number of patients with tobacco use
Time Frame: Baseline
Number of patients with tobacco use
Baseline
Number of Participants with concomitant diseases
Time Frame: Baseline
Number of Participants with concomitant diseases (diabetes Miletus, dyslipidemia, arterial hypertension, osteopenia, osteoporosis, presence of rheumatologic disease, renal failure, and other relevant comorbidity)
Baseline
Numer of current and previous treatments
Time Frame: Baseline
Number of current and previous treatments for osteoarthritis and tendinopathy
Baseline
Affected percentage of torn tendon in cross-sectional area
Time Frame: Baseline
Affected percentage of torn tendon in cross-sectional area in case of tendinopathy
Baseline
Bilateral comparison of affected tendon cross-sectional surface
Time Frame: Baseline
Bilateral comparison of affected tendon cross-sectional surface in mm2 on ultrasound
Baseline
Kellgren-Lawrence
Time Frame: Baseline
Baseline Kellgren-Lawrence grade in case of osteoarthritis. I: Mild to IV: Severe
Baseline
Number of patients with post-traumatic osteoarthritis
Time Frame: Baseline
Number of patients with post-traumatic osteoarthritis
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Adrien Schwitzguebel

Investigators

  • Principal Investigator: Adrien Schwitzguébel, MD., Hôpital de La Providenc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2023

Primary Completion (Anticipated)

January 1, 2025

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

January 24, 2022

First Submitted That Met QC Criteria

December 14, 2022

First Posted (Estimate)

December 21, 2022

Study Record Updates

Last Update Posted (Estimate)

December 21, 2022

Last Update Submitted That Met QC Criteria

December 14, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3.0.10.2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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