Intra-articular Adipose Tissue Injections for Osteoarthritis

A Randomized, Controlled Study to Evaluate the Efficacy of Intra-articular, Autologous Adipose Tissue Injections for the Treatment of Mild-to-Moderate Osteoarthritis

A new generation of "minimally manipulated" regenerative treatments are being offered at clinics across the country, but there is no strong efficacy data to support their use. The purpose of this study is to estimate the effect size of the treatment by comparing the efficacy of autologous fat to the current standard of care treatment, hyaluronic acid (HA). As a secondary aim, we will test for preliminary evidence of efficacy of autologous fat vs. HA and determine how these treatments effect the biochemical environment of the knee by comparing pre-injection and post-injection synovial fluid biomarker profiles.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Biological: Autologous adipose tissue injection; Drug: Hyaluronic Acid

Detailed Description

In recent years, fat treatments administered for structural reconstruction, repair, or replacement are being increasingly offered at clinics across the country. These treatments contain both autologous cells that are often referred to as "stem cells" or "MSCs" and extra-cellular matrix (ECM). Cell therapies containing ECM are thought to have the following advantages over treatments prepared using enzymatic digestion: (1) preservation of the stromal vascular niche, which allows time-release of the regenerative factors; (2) release of bioactive molecules by exosomes, which have been demonstrated to be significantly greater in mechanically processed fat than enzymatically processed fat; and (3) maintenance of the structural and morphologic unit, which is thought to increase cell efficacy by making the cells more resilient to the harsh conditions in the recipient environment. Case reports investigating the use of autologous fat treatments show promise, but a number of questions remain unanswered. Agents injected into the joint tend to be quickly cleared from the body and ECM itself has the potential to produce inflammatory signals and induce osteoarthritis.

This study will use a Hyaluronic acid (HA) as an active control, which is the standard of care for pain associated with osteoarthritis. The use of HA as an active control for autologous cell-based therapies is well established and is the best option given the need to aspirate fat tissue from patients who will be receiving the study treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Keck Medicine of USC
      • Contact: William Fang; Phone Number: 323-442-6959; Email: williahf@usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 45 to 75, inclusive
2. Normal axial alignment
3. X-ray, Kellgren-Lawrence OA grade 2 - 3, inclusive
4. WOMAC-pain: Between 9 and 19, inclusive
5. Willingness to participate all scheduled follow-ups
6. Willingness to refrain from taking NSAIDs, level 2 analgesics, and opioids for the course of the study
7. BMI < 40

Exclusion Criteria:

1. Pregnant or lactating
2. Intra-articular injection within 3 months of treatment
3. Inflammatory arthritis
4. Any disease or active drug use that significantly compromises coagulation
5. Significant damage and/or tears of the ACL or other supporting tissues
6. Prior knee surgery in the last 6 months in the knee that will be injected
7. Active tobacco use
8. Active alcohol or substance abuse within 6 months of study entry
9. Known hypersensitivity (allergy) to hyaluronan (sodium hyaluronate) preparations
10. Knee joint infections, skin diseases or infections in the area of the injection site
11. Diabetes
12. Active inhaler use
13. Any medical condition, which in the opinion of the clinical investigator, would interfere with the treatment or outcome evaluation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous adipose tissue knee injection; Fat will be removed from the abdomen and processed using the Lipogems device. Approximately 5ml of the microfragmented fat product will be injected into the knee joint.	Biological: Autologous adipose tissue injection; 20ml to 40ml of subcutaneous adipose tissue will be aspirated from the abdomen. Adipose tissue will be processed using the Lipogems device, a closed-loop processing device used in medical procedures involving the harvesting, concentrating and transferring of autologous adipose tissue. The resulting fat product will be delivered locally via ultrasound-guided, intra-articular injection.; Other Names: Lipogems, Microfragmented fat
Active Comparator: Hyaluronic Acid knee injection; Hyaluronic Acid - Synvisc-One®: A high molecular weight sodium hyaluronate (HA). HA is an FDA approved, standard of care treatment.	Drug: Hyaluronic Acid; Synvisc-One® is a high molecular weight sodium hyaluronate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pain items of then Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-A)	WOMAC-A is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain.	Change from baseline WOMAC score at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Reported Outcomes Measurement Information System 29-item (PROMIS®-29)	A collection of 4-item short forms assessing anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and ability to participate in social roles and activities as well as a single pain intensity item.	Change from baseline in PROMIS-29 from baseline to 6 months
Western Ontario and McMaster Universities Osteoarthritis Index	WOMAC is a widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness, and physical functioning of the joints.	Change from baseline in PROMIS-29 from baseline to 6 months
Clinical Anchors	Clinical anchors will be used to identify minimal important differences in treatment groups	Clinical anchors from baseline to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Synovial fluid analysis	Selected OA biomarker profiles that define different OA phenotypes predict the responses to autologous adipose tissue injections	Baseline, 6 weeks and 6 months
Short-term clinical evaluation - WOMAC	WOMAC questionnaire will be administered at the 6-week follow-up	Change from baseline at 6 weeks
Short-term clinical evaluation - PROMIS	PROMIS questionnaire will be administered at the 6-week follow-up	Change from baseline at 6 weeks
Force Plate Analysis	Balance will be assessed using a proprietary force plate system at baseline, 6 weeks and 6 months.	Assessment and change from baseline to 6 weeks and 6 months

Collaborators and Investigators

• Sponsor: University of Southern California
• Investigators: Principal Investigator: C.Thomas Vangsness, MD, Keck School of Medicine of USC

Publications and helpful links

General Publications

• Jones IA, Wilson M, Togashi R, Han B, Mircheff AK, Thomas Vangsness C Jr. A randomized, controlled study to evaluate the efficacy of intra-articular, autologous adipose tissue injections for the treatment of mild-to-moderate knee osteoarthritis compared to hyaluronic acid: a study protocol. BMC Musculoskelet Disord. 2018 Oct 24;19(1):383. doi: 10.1186/s12891-018-2300-7.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: July 28, 2017
• First Submitted That Met QC Criteria: August 6, 2017
• First Posted (Actual): August 8, 2017

Study Record Updates

• Last Update Posted (Actual): October 3, 2019
• Last Update Submitted That Met QC Criteria: October 2, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: HS-17-00365

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No