Nutrition Impact on PRGF Treatment for Tendinopathy (NUTRITENDON)

Nutrition as a Risk Factor and Predictor of Treatment Outcome With Plasma Rich Growth Factors for Shoulder Tendinopathy

Given the close correlation reported in the literature between onset and progression of tendon pathology in subjects affected by the alteration of metabolic disorders such as obesity, diabetes mellitus and lipidic metabolic alterations, with the present study the association between the nutritional state, metabolic profile and clinical outcome of patients following treatment with blood-derived orthobiological for shoulder tendinopathies will be evaluated.

The primary aim of this study is to identify the proportion of tendinopatic patients responsive and non-responsive to treatment with "Platelet rich growth factors" PRGF at six months follow up and the correlation with their nutritional status.

Study Overview

• Status: Recruiting
• Conditions: Shoulder Tendinopathy; Metabolic Alterations
• Intervention / Treatment: Biological: Platelet rich growth factor injection (autologous product)

Detailed Description

This is a single-center, observational study with an additional procedure (extra blood sampling routine, food questionnaires, anthropometric measurements for the evaluation of nutritional status), prospective, uncontrolled.

Male and female patients, between 18 and 70 years old suffering from tendinopathy of the shoulder who undergo conservative regenerative medicine procedures with autologous PRGF material at the IRCCS Galeazzi-Sant'Ambrogio Hospital of Milan and participants in the observational study "Use of Patient- Reported Outcome Measures (PROMs), objective clinical assessments and biomolecular technologies for monitoring patients undergoing treatments regenerative medicine" [REGAIN] will be enrolled for this study.

46 patients will be needed:

1. 23 subjects with body mass index (BMI) between 18.5 and 25 therefore considered normal weight, who undergo treatment with PRGF;
2. 23 subjects with BMI values that exceed the considered range normal weight, therefore with BMI>25, who undergo the PRGF treatment.

The general aim of the present study is to evaluate the correlation between the nutritional status of patients, the characteristics of the orthobiological product used for the treatment of shoulder tendon pathology and clinical outcomes after one-step conservative regenerative medicine treatment with PRGF in order to identify the ideal nutritional conditions to obtain the best clinical outcome from this type of treatment.

The primary objective of this study is to identify the proportion of tendinopatic patients responsive and non-responsive to treatment with orthobiological "Platelet rich growth factors" PRGF at six month follow up and the correlation with their nutritional status. To this end, responsive patients and non-responsive will be identified on the basis of the results of the VAS, ASES, Quick Dash, SPADI, WOOS scores, and Work index.

The secondary objectives of the study will be:

1) to Identify the proportion of responsive and non-responsive patients presenting shoulder tendinopathy to treatment with orthobiological "Platelet rich growth factors" PRGF at two and twelve months follow up and the correlation with their nutritional status. For this purpose, responsive and non-responsive patients will be identified on the basis of the results of the VAS, ASES, Quick Dash, SPADI scores, WOOS, and Work index.

Characterization of the PRGF product used for the treatment of each patient that will occur by qualitative and quantitative analysis of the content in extracellular vesicles, analysis of a panel of cytokines, chemokines and growth factors linked to inflammation and correlated to the state nutritional information of patients (e.g. resistin, P-selectin, interleukins etc.).

• Study Type: Observational
• Enrollment (Estimated): 52

Contacts and Locations

• Study Contact: Name: Paola De Luca, PhD; Phone Number: +39 3921385179; Email: deluca.paola@grupposandonato.it
• Study Contact Backup: Name: Michela Taiana, PhD; Phone Number: +39 3335952857; Email: michelamaria.taiana@grupposandonato.it

Study Locations

• Italy
  • Milan, Italy, 20173
    • Recruiting
    • I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
    • Contact: Elena Cittera; Phone Number: 00390283502224; Email: elena.cittera@grupposandonato.it
    • Principal Investigator: Paola De Luca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Male and female patients, between 18 and 70 years old suffering from shoulder tendinopathy undergoing a conservative regenerative medicine procedure with autologous PRGF at the IRCCS Galeazzi-Sant'Ambrogio Hospital of Milan and participants at the observational study "Use of patients- Reported Outcome Measures (PROM), objective clinical assessments and biomolecular technologies for monitoring patients undergoing treatments regenerative medicine" [REGAIN] will be enrolled for this study.

46 patients will be needed:

1. 23 subjects with body mass index (BMI) between 18.5 and 25 therefore considered normal weight, who undergo treatment with PRGF;
2. 23 subjects with BMI values that exceed the considered range normal weight, therefore with BMI>25, who undergo the PRGF treatment.

Description

Inclusion Criteria:

• Male and female
• Age ≥18 years and ≤ 70 years
• Patients presenting shoulder tendinopathy
• Signing of the Informed Consent of the Regain observational study
• Signature of informed consent of the present study.

Exclusion Criteria:

• Pregnancy (ascertained by self-declaration), breastfeeding
• Inability to follow the study protocol
• Heart, kidney, oncological disease
• Neuropsychiatric disease
• Other conditions that, at the discretion of the investigator or physician, exclude enrollement

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal weight patients; 23 subjects with body mass index (BMI) between 18.5 and 25 therefore considered normal weight, who undergo treatment with PRGF.	Biological: Platelet rich growth factor injection (autologous product); All patients will undergo two PRGF injections, one at recruitment and one 14 days after the first injection. The injection site will be the shoulder with tendinopathy.
Over weight patients; 23 subjects with BMI values that exceed the considered range normal weight, therefore with BMI>25, who undergo the PRGF treatment	Biological: Platelet rich growth factor injection (autologous product); All patients will undergo two PRGF injections, one at recruitment and one 14 days after the first injection. The injection site will be the shoulder with tendinopathy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder and non-responder patient identification at 6 months follow-up.	The primary objective of this study is to identify the proportion of responder and non-responder patients with shoulder tendinopathy to treatment with orthobiological "Platelet rich growth factors" PRGF at six month follow up. Responsive and non-responsive patients will be identified on the basis of the results of the VAS, ASES, Quick Dash, SPADI, WOOS scores, and Work index.	0-24 months
Identification of nutritional status of responder and non-responder patients: complete blood count	Complete blood count (cell number/dl)	0-24 months
Identification of nutritional status of responder and non-responder patients: blood glucose	Blood glucose (mg/dl)	0-24 months
Identification of nutritional status of responder and non-responder patients: Hemoglobin A1C (HbA1c)	Hemoglobin A1C (HbA1c): mmol/mol	0-24 months
Identification of nutritional status of responder and non-responder patients: urea	Urea: mg/dl	0-24 months
Identification of nutritional status of responder and non-responder patients: creatinine	Creatinine: mg/dl	0-24 months
Identification of nutritional status of responder and non-responder patients: siderosis	siderosis: ug/dl	0-24 months
Identification of nutritional status of responder and non-responder patients: tryglicerides	tryglicerides (mg/dl)	0-24 months
Identification of nutritional status of responder and non-responder patients: cholesterol	Cholesterol (mg/dl)	0-24 months
Identification of nutritional status of responder and non-responder patients: Cholesterol HDL	Cholesterol HDL (mg/dl)	0-24 months
Identification of nutritional status of responder and non-responder patients: Glutamate-oxaloacetate transaminase	Glutamate-oxaloacetate transaminase: (U/l)	0-24 months
Identification of nutritional status of responder and non-responder patients: Glutamate-pyruvate transaminase	Glutamate-pyruvate transaminase: (U/l)	0-24 months
Identification of nutritional status of responder and non-responder patients: gamma GT	Gamma GT: U/l	0-24 months
Identification of nutritional status of responder and non-responder patients: calcium	Calcium: mg/dl	0-24 months
Identification of nutritional status of responder and non-responder patients: Vitamin D (25 OH)	Vitamin D (25 OH): ng/ml	0-24 months
Identification of nutritional status of responder and non-responder patients: ferritin	Ferritin (ng/ml)	0-24 months
Identification of nutritional status of responder and non-responder patients:	C reactive protein: (mg/dl)	0-24 months
Identification of nutritional status of responder and non-responder patients: thyroid stimulating hormone (TSH)	thyroid stimulating hormone (TSH): uIU/ml	0-24 months
Identification of nutritional status of responder and non-responder patients: Insulin	Insulin: uU/ml	0-24 months
Identification of nutritional status of responder and non-responder patients: Folates	Folates (ng/ml)	0-24 months
Identification of nutritional status of responder and non-responder patients: vitamin B 12	Vitamin B 12 (pg/ml)	0-24 months
Anthropometric measurement: weight	weight (kg) measurement	0-24 months
Anthropometric measurement: height	height (m) measurement	0-24 months
Anthropometric measurement: waist circumference	waist circumference (cm) measurement	0-24 months
Anthropometric measurement: arm circumference measurements	arm circumference measurements (cm)	0-24 months
Anthropometric measurement: biceps folds measurement	biceps folds measurement (mm)	0-24 months
Anthropometric measurement: triceps folds measurement	triceps folds measurement (mm)	0-24 months
Anthropometric measurement: subscapular folds measurement	subscapular folds measurement (mm)	0-24 months
Anthropometric measurement: suprailiac folds measurement	suprailiac folds measurement (mm)	0-24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder and non-responder patient identification at 2 months follow-up.	The secondary objectives of the study will be: to Identify the proportion of patients with shoulder tendinopathy responsive and non-responsive to treatment with orthobiological "Platelet rich growth factors" PRGF at two months follow up. For this purpose, responsive and non-responsive patients will be identified on the basis of the results of the VAS, ASES, Quick Dash, SPADI scores, WOOS, and Work index.	2-26 months
Responder and non-responder patient identification at 12 months follow-up.	The secondary objectives of the study will be: to Identify the proportion of patients with shoulder tendinopathy responsive and non-responsive to treatment with orthobiological "Platelet rich growth factors" PRGF at twelve months follow up. For this purpose, responsive and non-responsive patients will be identified on the basis of the results of the VAS, ASES, Quick Dash, SPADI scores, WOOS, and Work index.	12-36 months
The Platelet rich growth factors "PRGF" product used for the treatment of each patient will be characterizated: extracellular vesicles count	extracellular vesicles count: number/ml	24-26 months
The PRGF product used for the treatment of each patient will be characterizated: extracellular vesicles marker quantification	Identification of extracellular vesicles markers: Arbitrary Fluorescence Unit	24-26 months
The PRGF product used for the treatment of each patient will be characterizated- quantitative analysis of cytokines: CXCL8	Quantitative analysis of cytokines (CXCL8): pg/ml	24-26 months
The PRGF product used for the treatment of each patient will be characterizated- quantitative analysis of growth factors: G-CSF	Quantitative analysis of growth factors: G-CSF (pg/ml)	24-26 months
The PRGF product used for the treatment of each patient will be characterizated- quantitative analysis of resistin	Quantitative analysis of resistin: pg/ml	24-26 months
The PRGF product used for the treatment of each patient will be characterizated- quantitative analysis of P-selectin	Quantitative analysis of P-selectin: pg/ml	24-26 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS	VAS: Visual analogue scales for grading of pain. The VAS ranges from 0 (no pain) to 10 (worst pain) ((consists of a 10 cm line with 10 mm (0.01 cm) to each point of the scale and two end-points representing no pain and worst possible pain, where 0 = no pain, 1-3 = mild, 4-6 = moderate and 7-10 = severe pain))	2-36 months
ASES SCORE	ASES (American Shoulder and Elbow Surgeons) Score: ASES score ranges from 0 to 100, with 0 the lowest level of function and 100 the highest level of function	2-36 months
Quick Dash Score	Quick Dash (Disabilities of Arm, Shoulder and Hand) score. The possible score ranges from 0 to 100 points. 0 points represent a complete, unrestricted function of the upper extremities, while 100 points represent the greatest possible functional impairment.	2-36 months
SPADI scores	SPADI (Shoulder Pain and Disability Index) scores. It evaluates pain and functional activities. Pain scale: 0 = no pain and 10 = the worst pain imaginable. Disability scale: 0 = no difficulty and 10 = so difficult it requires help. The means of the two subscales are averaged to produce a total score ranging from 0 (best) to 100 (worst).	2-36 months
WOOS Index	WOOS (Western Ontario Osteoarthritis of the Shoulder) index. 0% is the worst possible result and 100% is the best possible results.	2-36 months
WORC Index	The WORC (Western Ontario Rotator Cuff) Index, is a disease-specific quality of life questionnaire, evaluating the change in symptoms and functional ability, specific to a RC tendinopathy. Total final WORC scores can, therefore, range from 0% (lowest functional status level) to 100% (the highest functional status)	2-36 months

Collaborators and Investigators

• Sponsor: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2024
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Estimated): August 5, 2024

Study Record Updates

• Last Update Posted (Estimated): August 5, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: nutritional status; orthobiologics; responder and non-responder patients; Platelet rich growth factors
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Tendon Injuries; Tendinopathy; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: NUTRITENDON; 5xmille 2021CUPC43C2200237000 (Other Grant/Funding Number: Italian Ministry of health); L1054 Ricerca corrente (Other Grant/Funding Number: Italian Ministry of health)

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