Mesenchymal Stem Cell Therapy for Knee Osteoarthritis

NCT05288725 | Unknown Phase 1 FDA Drug FDA Device

• 1 other identifier: NGRM-001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

The study is a multicentered, randomized, double-blinded, placebo-controlled study conducted on the unilateral knee of 120 patients. The study compares the effectiveness of an injection of a mesenchymal stem cell preparation from autologous bone marrow aspirate (BMA) to a corticosteroid control for knee osteoarthritis. WOMAC, VAS pain scores, and MRI will be used for assessment. The study will be conducted at 3 sites in the United States.

Conditions

Osteoarthritis, Knee

Keywords

Osteoarthritis; Knee Osteoarthritis; Knee Pain; Bone Marrow Aspirate; Mesenchymal Stem Cells; Cell Therapy; Corticosteroid; Regenerative Medicine; Functional Improvement

Outcome Measures

Primary Outcomes (7)

• Change from Baseline Western Ontario McMaster University Osteoarthritis Index (WOMAC) at 3 months

  The Western Ontario and McMaster Universities Osteoarthritis Index 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. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The minimum clinically important difference (MCID) for this parameter is ≥ 10.

  3 months

• Change from Baseline Western Ontario McMaster University Osteoarthritis Index (WOMAC) at 6 months

  The Western Ontario and McMaster Universities Osteoarthritis Index 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. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The minimum clinically important difference (MCID) for this parameter is ≥ 10.

  6 months

• Change from Baseline Western Ontario McMaster University Osteoarthritis Index (WOMAC) at 12 months

  The Western Ontario and McMaster Universities Osteoarthritis Index 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. The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The minimum clinically important difference (MCID) for this parameter is ≥ 10.

  12 months

• Change from Baseline Visual Analog Score (VAS) at 3 months

  The pain VAS is a unidimensional scale of pain that is widely used and well validated in diverse groups of adult patients. The horizontal scale will be anchored by "no pain" (0) with "worst imaginable pain" (10) being at the opposite extreme. The minimum clinically important difference (MCID) for this measure is VAS ≥ 2

  3 months

• Change from Baseline Visual Analog Score (VAS) at 6 months

  The pain VAS is a unidimensional scale of pain that is widely used and well validated in diverse groups of adult patients. The horizontal scale will be anchored by "no pain" (0) with "worst imaginable pain" (10) being at the opposite extreme. The minimum clinically important difference (MCID) for this measure is VAS ≥ 2

  6 months

• Change from Baseline Visual Analog Score (VAS) at 12 months

  The pain VAS is a unidimensional scale of pain that is widely used and well validated in diverse groups of adult patients. The horizontal scale will be anchored by "no pain" (0) with "worst imaginable pain" (10) being at the opposite extreme. The minimum clinically important difference (MCID) for this measure is VAS ≥ 2

  12 months

• Magnetic Resonance Imaging (MRI) Evaluation

  Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body in both health and disease. MRI scanners use strong magnetic fields, radio waves, and field gradients to generate images of the inside of the body.

  Baseline and 12 months

Secondary Outcomes (12)

• Change from baseline measure of Fall Risk Functional Testing at 3 months

  3 months

• Change from baseline measure of Fall Risk Functional Testing at 6 months

  6 months

• Change from baseline measure of Fall Risk Functional Testing at 12 months

  12 months

• Change from baseline measure of Frailty Functional Testing at 3 months

  3 months

• Change from baseline measure of Frailty Functional Testing at 6 months

  6 months

Study Arms (4)

Intra-articular injection with Bone Marrow Derived Mesenchymal Stem Cells (MSCs)

EXPERIMENTAL

Participants will undergo a bone marrow aspirate procedure. Participants will receive a single intra-articular injection of NGRM-001 on treatment day.

Biological: Bone Marrow Derived MSCs; Device: Bone Marrow Aspirate

Subchondral injection with Bone Marrow Derived MSCs

EXPERIMENTAL

Participants will undergo a bone marrow aspirate procedure. Participants will receive a single subchondral injection of NGRM-001 on treatment day.

Biological: Bone Marrow Derived MSCs; Device: Bone Marrow Aspirate

Combined Intra-articular and Subchondral injection with Bone Marrow Derived MSCs

EXPERIMENTAL

Participants will undergo a bone marrow aspirate procedure. Participants will receive a single combined intra-articular and subchondral injection of NGRM-001 on treatment day.

Biological: Bone Marrow Derived MSCs; Device: Bone Marrow Aspirate

Corticosteroid injection

ACTIVE COMPARATOR

Subjects in the corticosteroid group will undergo a mock bone marrow aspirate procedure. Participants will receive a single intra-articular injection of corticosteroid on treatment day.

Drug: Corticosteroid; Device: Bone Marrow Aspirate

Interventions

Bone Marrow Derived MSCs BIOLOGICAL

Autologous bone marrow aspirate (BMA) is an orthobiologic injection used in knee osteoarthritis therapy. Bone marrow aspirate is harvested from the posterior superior iliac crest (PSIS) of the spine using the Marrow Cellutions kit. BMA will be injected into the knee using ultrasound guidance.

Also known as: Bone Marrow Aspirate, Marrow Cellutions

Combined Intra-articular and Subchondral injection with Bone Marrow Derived MSCs; Intra-articular injection with Bone Marrow Derived Mesenchymal Stem Cells (MSCs); Subchondral injection with Bone Marrow Derived MSCs

Corticosteroid DRUG

The corticosteroid is prepared in a 10 ml syringe by combining 1-2 mL Kenalog \[40 mg/dL\], 6-8 mL sterile normal saline, 3-4 mL Ropivicaine 1%.

Also known as: Kenalog

Corticosteroid injection

Bone Marrow Aspirate DEVICE

The Marrow Cellutions kit is an FDA approved device for harvesting bone marrow aspirate.

Combined Intra-articular and Subchondral injection with Bone Marrow Derived MSCs; Corticosteroid injection; Intra-articular injection with Bone Marrow Derived Mesenchymal Stem Cells (MSCs); Subchondral injection with Bone Marrow Derived MSCs

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must be willing and able to provide written informed consent.
• Healthy, non-smoking, males and females.
• Negative Pregnancy test.
• Body weight \> 45 kg and Body Mass Index (BMI) between 18 and 40 kg/m2 (i.e., subjects with a BMI \>40 and \<18 will be excluded).
• No clinically significant abnormal findings on blood pressure, heart rate, physical examination, clinical laboratory tests, or Electrocardiogram (ECG). See details below:
• Heart Rate (HR) \>60 and \<100 bpm
• Systolic Blood Pressure (BP) \>90 and \<170 mmHg
• Diastolic BP \>60 and \<80 mmHg
• Pulse oximetry ≥95% at room air
• Temperature: normal
• Laboratory measures within normal range
• Liver enzymes \<2 x Upper Limit of Normal (ULN)
• Normal bilirubin
• Normal Pain Threshold (PT) / International Normalized Ratio (INR)
• Estimated Glomerular Filtration Rate (eGFR) \>60 ml/min

You may not qualify if:

• Tibia on femur subluxation greater than 1mm. Varus or valgus number greater than 9°.
• Intra-articular injection to affected knee within 6 weeks of BMA injection
• Subjects who have had recent administration of intra- articular injection (e.g. corticosteroid, viscosupplement, platelet-rich plasma (PRP), or any other stem cell therapy) within the last 3 months prior to the experimental therapy.
• Subjects who have had recent systemic (oral (PO), intravenous (IV) and/or intramuscular (IM) within 6 weeks of treatment) administration of corticosteroids; including subjects who are likely to need or who are currently on systemic steroids (e.g., asthma)
• Subjects with a BMI of \>40 and \<18 will be excluded.
• Fever, active infection and ongoing infectious diseases, including HIV and hepatitis
• Clinically significant diabetes (HGB A1C \>7%), cardiovascular (stable cardiovascular (CV) disease as indicated by treating cardiologist within 30 days of enrollment and/or an ejection fraction of \<55%), hepatic (Pugh score of Class A or less than 6), or renal disease (Stage 1 or more severe).
• Malignancy of the blood such as leukemia or lymphoma or those malignancies which are not \> 5 years post treatment including prostate cancer, breast cancer, thyroid cancer, kidney cancer or lung cancer. Subjects with an active malignancy, or subjects with a history of any malignancy (e.g., including in situ, basal cell, etc.) will be excluded.
• Use of anti-rheumatic medications, including methotrexate and other anti-metabolites.
• Patients that are chronically taking Plavix, Coumadin and other anticoagulants for stroke/myocardial infarction/thromboembolic phenomena prevention, and/or Pradaxa, Xarelto, Mylanta, Fish Oil, Elmiron, Cipro, Levaquin, Quinolones, Ibuprofen, aspirin, Naproxen, CBD oil, Turmeric, or Meloxicam.
• Current chemo or radiation therapy
• Current drug or alcohol use disorder
• Subjects with h/o noncompliance or serious emotional disabilities, and/or any thought disorder, etc. will be excluded
• History of severe anemia or bleeding disorders (infectious arthritis, hemophilic arthropathy, Charcot's knee) (Anemia for the study is defined as Hgb 12 g/dL.)
• History of severe metabolic bone disease (osteoporosis, osteomalacia, rickets, osteitis fibrosa cystica, Paget's disease of bone) (Metabolic bone disease is osteoporosis diagnosed by DEXA scan, Leukemia, aplastic anemia or bone Metastasis.)

Sponsors & Collaborators

• Next Generation Regenerative Medicine LLC: lead

Study Sites (3)

Bluetail Medical Group

Chesterfield, Missouri, 63005, United States

Location

Scarpone Sports Regenerative

Steubenville, Ohio, 43952, United States

Location

Albano Clinic

Salt Lake City, Utah, 84121, United States

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Adrenal Cortex Hormones; Triamcinolone Acetonide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Michael A Scarpone, D.O.

  Next Generation Regenerative Medicine LLC

  PRINCIPAL INVESTIGATOR

• James G Unnerstall

  Next Generation Regenerative Medicine LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Corticosteroid as control both participant and investigator blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2022
• First Posted: March 21, 2022
• Study Start: August 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 21, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)