Oral Supplementation Compared With Hyaluronic Acid Infiltration in Rotator Cuff Tendinopathies

NCT06379997 | Recruiting DMC

• 1 other identifier: SANTA LUCIA IRCCS
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The present study aims to investigate the effectiveness of oral supplementation with a nutraceutical containing Collagen, Hyaluronic Acid, Vitamin C, and Manganese in functional outcome and pain reduction in cases of shoulder rotator cuff tendinopathy compared to a cycle of intra-articular hyaluronic acid injections. The project involves the recruitment of 50 adult individuals presenting with shoulder pain and instrumental evidence of rotator cuff tendinopathy. All participants will receive one intra-articular injection of 1 ml of triamcinolone acetonide 40 mg. After the injection, participants will be divided into two groups according to Good Clinical Practice guidelines. One group will begin taking one vial per day for 56 days of an oral supplement containing Hyaluronic Acid, Collagen, Vitamin C, and Manganese (HA-COL) (Tendogenial®, B2Pharma) starting from the day following enrollment (Group 1). The other group will undergo a cycle of 3 intra-articular injections with hyaluronic acid (HA) (Hyalotend®, Fidia) (Group 2). The hypothesis is that oral supplementation with HA-COL may have the same efficacy as intra-articular hyaluronic acid treatment in reducing pain and improving shoulder functionality. Functional assessments will be conducted by a clinician unaware of the participants' group assignment. The following assessment scales will be used: Numeric Rating Scale (NRS) for pain (from 0 to 10), evaluating 3 aspects of pain: 1) pain at rest, 2) nocturnal pain, 3) pain during movement. Shoulder Disability Questionnaire (SDQ) for functionality. Assessments will be conducted at the following time points: T0) Before the administration of corticosteroid intra-articular injection (baseline). T1) Seven days after the start of HA-COL intake for Group 1 and before the first intra-articular HA injection for Group 2 (T1, seven days from T0). T2) At mid-cycle of oral HA-COL supplementation for Group 1 (28 days of intake) and seven days after the last HA injection for Group 2 (T2, 21 days from T1). T3) Follow-up at 28 days from T2, at the end of the 56-day oral treatment cycle for Group 1, and 28 days after the last injection for Group 2 (T3, 56 days from T0).

Conditions

Tendinitis of Shoulder; Hyaluronic Acid; Dietary Supplements; Shoulder Pain

Outcome Measures

Primary Outcomes (1)

• Numeric rating scale (NRS)

  Change from baseline NRS at 1 weeks and at 4 weeks and at 8 weeks. NRS is a 10-point scale grading the pain at rest, during movement and during night-time

  1) (T0 - baseline). 2) Before the first administration of intra-articular HA for Group 2 and at seven days from the initiation of HA-COL for Group 1 (T1, seven days from T0). 3) At seven days fo

Secondary Outcomes (1)

• Shoulder Disability Questionnaire (SDQ) for shoulder functionality

  1) (T0 - baseline). 2) Before the first administration of intra-articular HA for Group 2 and at seven days from the initiation of HA-COL for Group 1 (T1, seven days from T0). 3) At seven days fo

Study Arms (2)

Oral supplemention

ACTIVE COMPARATOR

Assumption of 1 vial/day starting from the day after enrollment for 56 days. This supplement contains Collagen, Hyaluronic Acid, Vitamin C, and Manganese.

Dietary Supplement: Collagen, Hyaluronic Acid, Vitamin C, and Manganese

Intra-articolar infiltration

ACTIVE COMPARATOR

Intra-articular injections of a viscous solution of sodium salt hyaluronic acid (500-730 kDa) in pre-filled 20 mg/2 ml syringes, 1/week for 3 weeks.

Drug: Intra-articular infiltration

Interventions

Collagen, Hyaluronic Acid, Vitamin C, and Manganese DIETARY_SUPPLEMENT

The Group 1 (G1) will begin taking a dietary supplement the day after enrollment.

Also known as: Tendogenial

Oral supplemention

Intra-articular infiltration DRUG

Group 2 (G2) will receive three intra-articular injections once per week for 3 weeks, without ultrasound guidance. The route of administration will be intra-articular via the posterior access route.

Also known as: Hyalotend

Intra-articolar infiltration

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Persistent shoulder pain lasting for at least 2 months unresponsive to conservative treatment (nonsteroidal anti-inflammatory drugs \[NSAIDs\] and rehabilitation)
• Ultrasound or MRI evidence of a rotator cuff lesion without complete tendon rupture
• Limited active range of motion (ROM) in the shoulder

You may not qualify if:

• Traumatic shoulder injury as the cause of pain
• History of shoulder dislocation, fracture, or previous shoulder surgery
• Presence of signs indicating ligamentous instability
• Severe shoulder arthrosis, adhesive capsulitis, or calcific tendinitis
• Previous infiltrative treatment with corticosteroids, hyaluronic acid, or collagen within the past 6 months
• Diagnosis of rheumatic or neoplastic diseases
• Ongoing therapy with anticoagulants
• Cervical radiculopathy
• Pregnancy
• History of heart, kidney, or liver failure
• Cognitive impairment

Sponsors & Collaborators

• I.R.C.C.S. Fondazione Santa Lucia: lead

Study Sites (1)

I.R.C.C.S. Fondazione Santa Lucia

Roma, RM, 00179, Italy

RECRUITING

Related Publications (29)

• Luime JJ, Koes BW, Hendriksen IJ, Burdorf A, Verhagen AP, Miedema HS, Verhaar JA. Prevalence and incidence of shoulder pain in the general population; a systematic review. Scand J Rheumatol. 2004;33(2):73-81. doi: 10.1080/03009740310004667.

  PMID: 15163107 BACKGROUND

• Greving K, Dorrestijn O, Winters JC, Groenhof F, van der Meer K, Stevens M, Diercks RL. Incidence, prevalence, and consultation rates of shoulder complaints in general practice. Scand J Rheumatol. 2012 Mar;41(2):150-5. doi: 10.3109/03009742.2011.605390. Epub 2011 Sep 21.

  PMID: 21936616 BACKGROUND

• Dabija DI, Gao C, Edwards TL, Kuhn JE, Jain NB. Genetic and familial predisposition to rotator cuff disease: a systematic review. J Shoulder Elbow Surg. 2017 Jun;26(6):1103-1112. doi: 10.1016/j.jse.2016.11.038. Epub 2017 Feb 2.

  PMID: 28162885 BACKGROUND

• Herrmann SJ, Izadpanah K, Sudkamp NP, Strohm PC. Tears of the rotator cuff. Causes--diagnosis--treatment. Acta Chir Orthop Traumatol Cech. 2014;81(4):256-66.

  PMID: 25137495 BACKGROUND

• Via AG, De Cupis M, Spoliti M, Oliva F. Clinical and biological aspects of rotator cuff tears. Muscles Ligaments Tendons J. 2013 Jul 9;3(2):70-9. doi: 10.11138/mltj/2013.3.2.070. Print 2013 Apr.

  PMID: 23888289 BACKGROUND

• Ackermann PW, Renstrom P. Tendinopathy in sport. Sports Health. 2012 May;4(3):193-201. doi: 10.1177/1941738112440957.

  PMID: 23016086 BACKGROUND

• Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials. Lancet. 2010 Nov 20;376(9754):1751-67. doi: 10.1016/S0140-6736(10)61160-9. Epub 2010 Oct 21.

  PMID: 20970844 BACKGROUND

• van der Worp H, van den Akker-Scheek I, van Schie H, Zwerver J. ESWT for tendinopathy: technology and clinical implications. Knee Surg Sports Traumatol Arthrosc. 2013 Jun;21(6):1451-8. doi: 10.1007/s00167-012-2009-3. Epub 2012 May 1.

  PMID: 22547246 BACKGROUND

• Osti L, Buda M, Buono AD, Osti R, Massari L. Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid. Muscles Ligaments Tendons J. 2016 Feb 13;5(4):270-5. doi: 10.11138/mltj/2015.5.4.270. eCollection 2015 Oct-Dec.

  PMID: 26958534 BACKGROUND

• Lee LC, Lieu FK, Lee HL, Tung TH. Effectiveness of hyaluronic acid administration in treating adhesive capsulitis of the shoulder: a systematic review of randomized controlled trials. Biomed Res Int. 2015;2015:314120. doi: 10.1155/2015/314120. Epub 2015 Jan 31.

  PMID: 25802845 BACKGROUND

• Salamanna F, Frizziero A, Pagani S, Giavaresi G, Curzi D, Falcieri E, Marini M, Abruzzo PM, Martini L, Fini M. Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes. Connect Tissue Res. 2015 Feb;56(1):35-43. doi: 10.3109/03008207.2014.979166. Epub 2014 Nov 13.

  PMID: 25333747 BACKGROUND

• Iwata H. Pharmacologic and clinical aspects of intraarticular injection of hyaluronate. Clin Orthop Relat Res. 1993 Apr;(289):285-91.

  PMID: 8472428 BACKGROUND

• Oliva F, Marsilio E, Asparago G, Frizziero A, Berardi AC, Maffulli N. The Impact of Hyaluronic Acid on Tendon Physiology and Its Clinical Application in Tendinopathies. Cells. 2021 Nov 9;10(11):3081. doi: 10.3390/cells10113081.

  PMID: 34831304 BACKGROUND

• Abate M, Schiavone C, Salini V. The use of hyaluronic acid after tendon surgery and in tendinopathies. Biomed Res Int. 2014;2014:783632. doi: 10.1155/2014/783632. Epub 2014 May 8.

  PMID: 24895610 BACKGROUND

• Franchi M, Trire A, Quaranta M, Orsini E, Ottani V. Collagen structure of tendon relates to function. ScientificWorldJournal. 2007 Mar 30;7:404-20. doi: 10.1100/tsw.2007.92.

  PMID: 17450305 BACKGROUND

• Hijlkema A, Roozenboom C, Mensink M, Zwerver J. The impact of nutrition on tendon health and tendinopathy: a systematic review. J Int Soc Sports Nutr. 2022 Aug 3;19(1):474-504. doi: 10.1080/15502783.2022.2104130. eCollection 2022.

  PMID: 35937777 BACKGROUND

• Boldt KS, Olson BL, Thiele RM. Effects of Collagen and Exercise on Tendon Properties and Pain: A Critically Appraised Topic. J Sport Rehabil. 2023 Sep 27;32(8):938-941. doi: 10.1123/jsr.2023-0115. Print 2023 Nov 1.

  PMID: 37758259 BACKGROUND

• Campos LD, Santos Junior VA, Pimentel JD, Carrega GLF, Cazarin CBB. Collagen supplementation in skin and orthopedic diseases: A review of the literature. Heliyon. 2023 Mar 28;9(4):e14961. doi: 10.1016/j.heliyon.2023.e14961. eCollection 2023 Apr.

  PMID: 37064452 BACKGROUND

• Kalman DS, Heimer M, Valdeon A, Schwartz H, Sheldon E. Effect of a natural extract of chicken combs with a high content of hyaluronic acid (Hyal-Joint) on pain relief and quality of life in subjects with knee osteoarthritis: a pilot randomized double-blind placebo-controlled trial. Nutr J. 2008 Jan 21;7:3. doi: 10.1186/1475-2891-7-3.

  PMID: 18208600 BACKGROUND

• Lopez-Vidriero E, Olive-Vilas R, Lopez-Capape D, Varela-Sende L, Lopez-Vidriero R, Til-Perez L. Efficacy and Tolerability of Progen, a Nutritional Supplement Based on Innovative Plasma Proteins, in ACL Reconstruction: A Multicenter Randomized Controlled Trial. Orthop J Sports Med. 2019 Feb 27;7(2):2325967119827237. doi: 10.1177/2325967119827237. eCollection 2019 Feb.

  PMID: 30834280 BACKGROUND

• Leon-Lopez A, Morales-Penaloza A, Martinez-Juarez VM, Vargas-Torres A, Zeugolis DI, Aguirre-Alvarez G. Hydrolyzed Collagen-Sources and Applications. Molecules. 2019 Nov 7;24(22):4031. doi: 10.3390/molecules24224031.

  PMID: 31703345 BACKGROUND

• Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann DF, Meza F, Millard RL, Deitch JR, Sherbondy PS, Albert A. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Opin. 2008 May;24(5):1485-96. doi: 10.1185/030079908x291967. Epub 2008 Apr 15.

  PMID: 18416885 BACKGROUND

• Noriega-Gonzalez DC, Drobnic F, Caballero-Garcia A, Roche E, Perez-Valdecantos D, Cordova A. Effect of Vitamin C on Tendinopathy Recovery: A Scoping Review. Nutrients. 2022 Jun 27;14(13):2663. doi: 10.3390/nu14132663.

  PMID: 35807843 BACKGROUND

• Ozgen M, Firat S, Sarsan A, Topuz O, Ardic F, Baydemir C. Short- and long-term results of clinical effectiveness of sodium hyaluronate injection in supraspinatus tendinitis. Rheumatol Int. 2012 Jan;32(1):137-44. doi: 10.1007/s00296-010-1577-0. Epub 2010 Jul 31.

  PMID: 20676646 BACKGROUND

• Croft P, Pope D, Zonca M, O'Neill T, Silman A. Measurement of shoulder related disability: results of a validation study. Ann Rheum Dis. 1994 Aug;53(8):525-8. doi: 10.1136/ard.53.8.525.

  PMID: 7944638 BACKGROUND

• Brindisino F, Pellicciari L, Lorusso M, Pennella D, Padua R, Di Bari M. Cross-cultural adaptation, reliability, and validity of the Italian version of the Shoulder Disability Questionnaire. Musculoskelet Sci Pract. 2020 Apr;46:102123. doi: 10.1016/j.msksp.2020.102123. Epub 2020 Jan 31.

  PMID: 32217269 BACKGROUND

• Chou WY, Ko JY, Wang FS, Huang CC, Wong T, Wang CJ, Chang HE. Effect of sodium hyaluronate treatment on rotator cuff lesions without complete tears: a randomized, double-blind, placebo-controlled study. J Shoulder Elbow Surg. 2010 Jun;19(4):557-63. doi: 10.1016/j.jse.2009.08.006. Epub 2009 Dec 5.

  PMID: 19963403 BACKGROUND

• Moghtaderi A, Sajadiyeh S, Khosrawi S, Dehghan F, Bateni V. Effect of subacromial sodium hyaluronate injection on rotator cuff disease: A double-blind placebo-controlled clinical trial. Adv Biomed Res. 2013 Nov 30;2:89. doi: 10.4103/2277-9175.122517. eCollection 2013.

  PMID: 24524035 BACKGROUND

• Byun SD, Park DH, Choi WD, Lee ZI. Subacromial Bursa Injection of Hyaluronate with Steroid in Patients with Peri-articular Shoulder Disorders. Ann Rehabil Med. 2011 Oct;35(5):664-72. doi: 10.5535/arm.2011.35.5.664. Epub 2011 Oct 31.

  PMID: 22506189 BACKGROUND

MeSH Terms

Conditions

Shoulder Pain

Interventions

Collagen; Hyaluronic Acid; Ascorbic Acid; Manganese

Condition Hierarchy (Ancestors)

Arthralgia; Joint Diseases; Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biopolymers; Polymers; Macromolecular Substances; Extracellular Matrix Proteins; Scleroproteins; Proteins; Amino Acids, Peptides, and Proteins; Glycosaminoglycans; Polysaccharides; Carbohydrates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Stefano Brunelli, MD

  I.R.C.C.S. Fondazione Santa Lucia, Roma, Italy

  STUDY DIRECTOR

Central Study Contacts

Stefano Brunelli, MD

CONTACT

0651501844; s.brunelli@hsantalucia.it

Noemi Gentileschi, MD

CONTACT

0651501845; n.gentileschi@hsantalucia.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Both study groups will undergo assessment using pain and functional scales by a clinician who is blinded to the treatment group
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD

Model Details: The enrolled patients will be randomized in two groups: treated with oral supplements (Group 1 - G1) or with intra-articular hyaluronic acid (Group 2 - G2)

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: April 23, 2024
• Study Start: August 10, 2024
• Primary Completion: November 1, 2025
• Study Completion: December 31, 2025
• Last Updated: August 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Proposals should be directed to the personal corrisponding author's mail address.

Locations

IT (1)