Epidemiology and Nutrition (Nutririsk)

Nutrition as a Risk Factor and Predictor of the Outcome of Orthobiological Treatments for Knee Osteoarthritis

The general purpose of this study is to evaluate the relation between the nutritional status of patients, the features of the orthobiologics products used for patients' treatment and the clinical outcomes after one-step conservative regenerative treatment for knee osteoarthritis.

Study Overview

• Status: Recruiting
• Conditions: Musculoskeletal Diseases; Osteoarthritis, Knee; Nutrition, Healthy

Detailed Description

The general purpose of this monocentric, observational with additional procedure (extra routine blood sampling, questionnaires and measurement of Nutritional status), prospective and non-controlled study is to evaluate the relation between the nutritional status of patients, the features of the orthobiologics products used for patients' treatment and the clinical outcomes after one-step conservative regenerative treatment (Platelete rich plasma and micro-fragmented adipose tissue injections) for knee osteoarthritis.The primary outcome of the study will be the identification of the proportion of responders and non-responders patients to the orthobiologic treatment (according to OMERACT-OARSI criteria) at 6-month follow-up. Another primary outcome will be the nutritional status identification of the same patients.

For these purposes the responder or non-responder patients will be identified based on the results of the Visual Analogue Scale (VAS) [the score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100; a higher score indicates greater pain intensity no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm)], Tegner-Lysholm Activity Scale and Knee Injury (Scores range from 0=worse disability to 100=less disability) and Osteoarthritis Outcome score (KOOS) (the score is a percentage score from 0 to 100, 0 representing extreme problems and 100 representing no problems) according to the parameters established by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) and Osteoarthritis Research Society International (OARSI) [they cannot be represented by a range of values]. The secondary outcomes of the study will be:

• the identification of the proportion of responders and non-responders patients to the orthobiologic treatment (according to OMERACT-OARSI criteria) at 2 and 12-month follow-up and of their related nutritional status;
• the characterization of the orthobiologic products used for the patient's treatment.

After the ethics committee approval, patients meeting the inclusion criteria undergoing conservative knee regenerative medicine treatments with orthobiologics and participating to the observational study "REGAIN" will be enrolled into the study. The PROMs will be completed by patients based on their clinical condition and on the specific treatment they will receive at the REGAIN Center. The aforementioned PROMs include but are not limited to:

- VAS, Tegner-Lysholm Activity Scale, KOOS. Patients will be asked to filled the PROMs at the time of the enrollment (before the treatment) and then at 2, 6 and 12 months after the treatment.

Blood and nutritional information will be collected only the day of the treatment to allow for evaluation of the possible association between patients' characteristics and treatment outcomes. Blood sampling will be performed to carry out the following laboratory analysis, in detail: complete blood count (cell number/dl), blood glucose (mg/dl), hemoglobin A1C (HbA1c) (mmol/mol), creatinine (mg/dl), Glutamic Oxaloacetic Transaminase (GOT) and Glutamic-Pyruvic Transaminase (GPT) (U/L), C reactive protein (mg/dl), triglycerides (mg/dl), total cholesterol(mg/dl), HDL(mg/dl).

In particular, for patients undergoing a Platelet Rich Plasma (PRP) treatment, a blood sample is already routinely harvested and therefore only an extra test tube will be added to test blood glucose (mg/dl), hemoglobin A1C (HbA1c) (mmol/mol), creatinine (mg/dl), GOT and GPT transaminases (U/L), C reactive protein (mg/dl), triglycerides (mg/dl), total cholesterol(mg/dl), HDL(mg/dl). For patients undergoing a treatment with microfragmented adipose tissue, an ad hoc blood collection will be carried out by filling two test tubes.

Nutritional information include anthropometric measurements, diet history and food consumption questionnaire (24h recall, "How much do i really eat?", Italian Mediterranea Index, anamnesi). Anthropometric measurements include weight (kg) and height (m), waist circumference (cm), arm circumference measurements (cm), biceps, triceps, subscapular and suprailiac folds measurement (mm) (plicometry) through the use of the skinfolder. It should be noted that the skinfolder is only one of the tools used to evaluate the patient's nutritional status, without diagnostic purposes and without the will to investigate anything about the device.

Concerning the orthobiologics characterization, PRP and microfragmented adipose tissue will undergo to different evaluations as per the observational study protocol "REGAIN".

In addition, for the purpose of this study, isolation and characterization of extracellular vesicles derived from PRP and micro fragmented adipose tissue will be performed, in order to deepen the orthobiologic characterization. The following techniques will be applied, where appropriate:

• Count and identification of cells from PRP and microfragmented adipose tissue (hemacytometer, nucleocounter, flow cytometry);
• Extracellular vesicle isolation, count and dimensional analysis (ultracentrifuge, Nanosights);
• Extracellular vesicle marker identification (flow cytometry).

These data will be analyzed for their possible association with nutritional status of the patient and clinical outcomes.

Regardless the specific protocol or investigation, the analysis will not include genomic DNA or diagnostic analysis. All samples (blood and tissues) will be analyzed at Istituto Ortopedico Galeazzi and destroyed at the end of the study. Total duration of this study is of 36 months after approval of Ethical Committee.

• Study Type: Observational
• Enrollment (Anticipated): 88

Contacts and Locations

Study Locations

• Italy
  • Italia
    • Milan, Italia, Italy
      • Recruiting
      • IRCCS Galeazzi orthopaedic institute
      • Contact: Elena Cittera; Phone Number: 0039 02 66214057; Email: mailto:elena.cittera@grupposandonato.it
      • Principal Investigator: Paola De Luca, post doc researcher

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients affected by knee osteoarthritis undergoing conservative regenerative medicine procedures with autologous material at IRCCS Istituto Ortopedico Galeazzi and participating to the observational study "REGAIN" will be enrolled for this study:

88 patients will be needed:

1. 22 subjects with body mass index (BMI) considered normal weight (≥18.5 and ≤25) undergo to Platelet-Rich Plasma (PRP) treatment;
2. 22 subjects with BMI>25 undergo to PRP treatment;
3. 22 subjects with BMI ≥18.5 and ≤25 undergo to microfragmented adipose tissue treatment;
4. 22 subjects with BMI >25 undergo to microfragmented adipose tissue treatment.

Description

Inclusion Criteria:

• males and females ≥18 and ≤ 65 years;
• presence of knee osteoarthritis;
• indication to regenerative medicine treatments PRP or microfragmented adipose treatment;
• participation to the observational study "REGAIN";
• patients with BMI ≥18.5;
• signature of Informed Consent for the study.

Exclusion Criteria:

• patients with BMI <18.5;
• patients who are not able to comply with the study schedule.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
subjects normal weight undergo to PRP treatment; subjects with body mass index (BMI) considered normal weight (≥18.5 and ≤25) undergo to Platelet-Rich Plasma (PRP) treatment.
subjects overweight undergo to PRP treatment; subjects with BMI values that exceed the normal weight range (BMI>25) undergo to PRP treatment.
subjects with normal weight undergo to microfragmented adipose tissue treatment; subjects with BMI within the considered normal weight range (≥18.5 e ≤25) and undergo to microfragmented adipose tissue treatment.
subjects overweight undergo to microfragmented adipose tissue treatment; subjects with BMI values that exceed the normal weight range undergo to microfragmented adipose tissue treatment. (BMI>25).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 months follow-up, responders and not responders	Identification of the proportion of responders and non-responders patients to the orthobiologic treatment (according to OMERACT-OARSI criteria) at 6-month follow-up.	6 months after treatment
Identification of the nutritional status of patients: Complete blood count	Complete blood count (cell number/dl)	10 minutes before the treatment
Identification of the nutritional status of patients: Blood glucose	Blood glucose (mg/dl) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood Hemoglobin A1C (HbA1c)	Hemoglobin A1C (HbA1c) (mmol/mol) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood creatinine	Creatinine (mg/dl) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood Glutamic-Oxaloacetic Transaminase GOT (U/L)	Glutamic-Oxaloacetic Transaminase GOT (U/L) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood Glutamate Pyruvate Transaminase GPT	Glutamate Pyruvate Transaminase GPT (U/L) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood C reactive protein	C reactive protein (mg/dl) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood Triglycerides	Triglycerides (mg/dl) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood total cholesterol	Total cholesterol (mg/dl) measurement	10 minutes before the treatment
Identification of the nutritional status of patients: blood High Density Lipoprotein HDL	High Density Lipoprotein HDL (mg/dl) measurement	10 minutes before the treatment
Anthropometric measurement: weight	weight (kg) measurement	10 minutes before the treatment
Anthropometric measurement: height	height (m) measurement	10 minutes before the treatment
Anthropometric measurement: waist circumference	waist circumference (cm) measurement	10 minutes before the treatment
Anthropometric measurement: arm circumference measurements	arm circumference measurements (cm)	10 minutes before the treatment
Anthropometric measurement: biceps folds measurement	biceps folds measurement (mm)	10 minutes before the treatment
Anthropometric measurement: triceps folds measurement	triceps folds measurement (mm)	10 minutes before the treatment
Anthropometric measurement: subscapular folds measurement	subscapular folds measurement (mm)	10 minutes before the treatment
Anthropometric measurement: suprailiac folds measurement	suprailiac folds measurement (mm)	10 minutes before the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2 months follow-up, responders and not responders	The identification of the proportion of responders and non-responders patients to the orthobiologic treatment (according to OMERACT-OARSI criteria) at 2 months follow-up	2 months after treatment
12 months follow-up, responders and not responders	The identification of the proportion of responders and non-responders patients to the orthobiologic treatment (according to OMERACT-OARSI criteria) at 12 months follow-up	12 months after treatment
The characterization of the orthobiologic products.	The characterization of the orthobiologic products used for the patient's treatment that include isolation and characterization of extracellular vesicles derived from PRP and micro fragmented adipose tissue.	15 minutes after the treatment

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Galeazzi

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: December 28, 2021
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Musculoskeletal Diseases
• Other Study ID Numbers: Nutririsk

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No