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.
