Can Vitamin C Reduce the Risk of Postoperative Shoulder Stiffness?

NCT04472000 | Terminated Phase 4

• 1 other identifier: 2020-00605
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

Brief Summary

Postoperative shoulder stiffness is a common complication after shoulder surgery (incidence 10-15%). The symptoms consist primarily in a painful impairment of the mobility of the glenohumeral joint, usually after initially good course. Cause and origin are not clear. Vitamin C is known as an inactivator of free radicals and plays a key role in building collagen tissue. Vitamin C thus has a modulating role in inflammatory reactions. Injured and ill people have been shown to have significantly increased vitamin C needs, which underlines this role. Evidence was also found that vitamin C has a positive influence on similar diseases such as the complex regional pain syndrome (CRPS, Morbus Sudeck) on the wrist and postoperative arthrofibrosis on the knee joint. The Investigators want to investigate whether vitamin C intake can positively influence the incidence and / or severity of postoperative shoulder stiffness after shoulder surgery. The primary objective of this study is to investigate the effect of vitamin C on the external rotational ability of the operated shoulder in the glenohumeral joint compared to the opposite side at 12 weeks post surgery. Secondary objectives of this study are to investigate other shoulder mobility tests, patient-reported outcomes (level of pain, ability/return to work, smoking habits), patient-reported questionnaires (Constant Score, Oxford shoulder score, DASH score) and the incidence of a frozen shoulder at 6, 12, 26, and 52 weeks post surgery. Total duration of study: 2.5 years.

Conditions

Shoulder Stiffness

Keywords

Vitamin C; pain; mobility; rotation; glenohumeral joint

Outcome Measures

Primary Outcomes (1)

• Difference between the external glenohumeral joint rotations of the operated shoulder and the opposite shoulder

  The primary endpoint of this study is the difference between the external glenohumeral joint rotations of the operated shoulder and the opposite shoulder ("Delta ∆"). The external glenohumeral joint rotation was chosen as primary measure for shoulder performance because this is the component of movement in the shoulder joint, which is the first and most severely impaired in postoperative shoulder stiffness and which normalizes as the last after the symptomatology subsides. Delta ∆ was chosen as an outcome measure, since the standard deviation of the external rotation capability in the population is very high. The external glenohumeral joint rotation of both shoulders is measured using a smartphone with the App "GetMyROM".

  12 weeks post surgery

Secondary Outcomes (11)

• Delta ∆ of the external glenohumeral joint rotation

  after 6, 26, and 52 weeks post surgery

• Delta ∆ of abduction

  after 6, 26, and 52 weeks post surgery

• Delta ∆ of internal rotation

  after 6, 26, and 52 weeks post surgery

• Delta ∆ of flexion

  after 6, 26, and 52 weeks post surgery

• Level of pain

  daily during the first 50 days post surgery, and at 12, 26, and 52 weeks post surgery as a criterion for the occurrence of postoperative frozen shoulder

Study Arms (2)

Vitamin C

EXPERIMENTAL

Patients who are assigned to the experimental treatment group will be given extended release capsules with 500 mg of ascorbic acid orally two times daily, packed in PET/PP-bottles identical as used for the licenced product.

Drug: Vitamin C

Placebo

PLACEBO COMPARATOR

The control intervention of this study consists of treatment with no active substance (placebo) but in the same schedule as the experimental treatment (verum).

Drug: Placebo

Interventions

Vitamin C DRUG

Study participants in the verum group receive one capsule of Burgerstein Vitamin C retard 500mg b.i.d. with treatment starting in the evening on the day of the operation for a total of 50 days.

Vitamin C

Placebo DRUG

The placebo group receives one placebo capsule b.i.d. with treatment starting in the evening on the day of the operation for a total of 50 days.

Placebo

Eligibility Criteria

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

You may qualify if:

• Informed Consent as documented by signature
• years or older at the time of informed consent signature
• Complication-free rotator cuff\* or shoulder arthroscopy\*\* with or without resection of the acromioclavicular joint at the orthopedics Sonnenhof. The rotator cuff operations are basically open or in mini-open technique, usually with additional tenotomy / tenodesis of the long biceps tendon.
• \* rotator cuff surgery can include tenotomy/tenodesis of long biceps tendon, intra-articular debridement with or without resection of the coracoacromial ligament and/or acromioplasty, biopsies, diagnostic arthroscopy
• \*\* Arthroscopic procedures include subacromial debridement (including partial resection of the coracoacromial ligament \& acromioplasty), diagnostic arthroscopy, tenotomy of the long biceps tendon, intra-articular debridement, resection of calcium depots for treatment of tendinitis calcarea, biopsies, stabilizations (only without postoperative immobilization)
• Sufficient knowledge of German to understand the patient information and informed consent, follow instructions by study personnel, and complete patient questionnaires \& diary

You may not qualify if:

• Contraindications to ascorbic acid or one of the excipients, e.g. known hypersensitivity or allergy to the investigational product
• Planned single or multiple intake of vitamin supplements during the study period, which results in an additional daily intake of \> 50 mg ascorbic acid
• Known pregnancy or breast feeding
• Known or suspected non-compliance, for example drug or alcohol abuse
• Inability to follow the procedures of the study, e.g. due to psychological disorders, dementia, etc.
• Participation in another interventional study within the 30 days preceding and during the present study
• Previous enrollment into the current study
• Enrollment of the investigator, his / her family members, employees and other dependent persons
• Current or previous frozen shoulder (no matter on which side)
• Pre-surgery on the affected shoulder joint (preoperative procedures include all procedures examined in this study, including all other procedures involving the glenohumeral joint and / or acromioclavicular joint. In addition, all interventions, which as a result, negatively influence the mobility of the shoulder with great likelihood up to the current time)
• Known current unstable medical problem on the not-affected shoulder joint according to the judgment of the investigator
• Taking a cortisone preparation or an immunomodulatory drug (for example methotrexate or similar)
• Alcoholism (defined as intake of more than 12g (women) or 24g (men) alcohol per day)
• Regular hemodialysis
• Known diabetes mellitus

Sponsors & Collaborators

• Lindenhofgruppe AG: lead

Study Sites (2)

Spital Aaberg

Aarberg, Canton of Bern, 3270, Switzerland

Location

Orthopädie Sonnenhof

Bern, Switzerland

Location

Related Publications (25)

• Cho CH, Song KS, Kim BS, Kim DH, Lho YM. Biological Aspect of Pathophysiology for Frozen Shoulder. Biomed Res Int. 2018 May 24;2018:7274517. doi: 10.1155/2018/7274517. eCollection 2018.

  PMID: 29992159 BACKGROUND

• Wong CK, Levine WN, Deo K, Kesting RS, Mercer EA, Schram GA, Strang BL. Natural history of frozen shoulder: fact or fiction? A systematic review. Physiotherapy. 2017 Mar;103(1):40-47. doi: 10.1016/j.physio.2016.05.009. Epub 2016 Jun 21.

  PMID: 27641499 BACKGROUND

• Kim DH, Kim YS, Kim BS, Sung DH, Song KS, Cho CH. Is frozen shoulder completely resolved at 2 years after the onset of disease? J Orthop Sci. 2020 Mar;25(2):224-228. doi: 10.1016/j.jos.2019.03.011. Epub 2019 Apr 2.

  PMID: 30952550 BACKGROUND

• Aim F, Klouche S, Frison A, Bauer T, Hardy P. Efficacy of vitamin C in preventing complex regional pain syndrome after wrist fracture: A systematic review and meta-analysis. Orthop Traumatol Surg Res. 2017 May;103(3):465-470. doi: 10.1016/j.otsr.2016.12.021. Epub 2017 Mar 4.

  PMID: 28274883 BACKGROUND

• Kim JH, Kim YC, Nahm FS, Lee PB. The Therapeutic Effect of Vitamin C in an Animal Model of Complex Regional Pain Syndrome Produced by Prolonged Hindpaw Ischemia-Reperfusion in Rats. Int J Med Sci. 2017 Jan 15;14(1):97-101. doi: 10.7150/ijms.17681. eCollection 2017.

  PMID: 28138314 BACKGROUND

• Chen S, Roffey DM, Dion CA, Arab A, Wai EK. Effect of Perioperative Vitamin C Supplementation on Postoperative Pain and the Incidence of Chronic Regional Pain Syndrome: A Systematic Review and Meta-Analysis. Clin J Pain. 2016 Feb;32(2):179-85. doi: 10.1097/AJP.0000000000000218.

  PMID: 25654537 BACKGROUND

• Fukushima R, Yamazaki E. Vitamin C requirement in surgical patients. Curr Opin Clin Nutr Metab Care. 2010 Nov;13(6):669-76. doi: 10.1097/MCO.0b013e32833e05bc.

  PMID: 20689415 BACKGROUND

• Behrend H, Lengnick H, Zdravkovic V, Ladurner A, Rudin D, Erschbamer M, Joerger M, Kuster M. Vitamin C demand is increased after total knee arthroplasty: a double-blind placebo-controlled-randomized study. Knee Surg Sports Traumatol Arthrosc. 2019 Apr;27(4):1182-1188. doi: 10.1007/s00167-018-5030-3. Epub 2018 Jun 28.

  PMID: 29955932 BACKGROUND

• Giladi AM, Dossett LA, Fleming SB, Abumrad NN, Cotton BA. High-dose antioxidant administration is associated with a reduction in post-injury complications in critically ill trauma patients. Injury. 2011 Jan;42(1):78-82. doi: 10.1016/j.injury.2010.01.104. Epub 2010 Feb 10.

  PMID: 20149369 BACKGROUND

• Rizzo JA, Rowan MP, Driscoll IR, Chung KK, Friedman BC. Vitamin C in Burn Resuscitation. Crit Care Clin. 2016 Oct;32(4):539-46. doi: 10.1016/j.ccc.2016.06.003. Epub 2016 Aug 2.

  PMID: 27600125 BACKGROUND

• Kleszczewski T, Modzelewska B, Lisowska A, Buzun L, Kleszczewska E. Levels of vitamin C In the blood plasma patients treated with coronary artery bypass grafting increases significantly after surgery. Biomed Pharmacother. 2017 Jan;85:527-530. doi: 10.1016/j.biopha.2016.11.060. Epub 2016 Nov 24.

  PMID: 27890433 BACKGROUND

• Lee GW, Yang HS, Yeom JS, Ahn MW. The Efficacy of Vitamin C on Postoperative Outcomes after Posterior Lumbar Interbody Fusion: A Randomized, Placebo-Controlled Trial. Clin Orthop Surg. 2017 Sep;9(3):317-324. doi: 10.4055/cios.2017.9.3.317. Epub 2017 Aug 4.

  PMID: 28861199 BACKGROUND

• Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. 2007 Jul;89(7):1424-31. doi: 10.2106/JBJS.F.01147.

  PMID: 17606778 BACKGROUND

• Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial. Lancet. 1999 Dec 11;354(9195):2025-8. doi: 10.1016/S0140-6736(99)03059-7.

  PMID: 10636366 BACKGROUND

• Traxer O, Huet B, Poindexter J, Pak CY, Pearle MS. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol. 2003 Aug;170(2 Pt 1):397-401. doi: 10.1097/01.ju.0000076001.21606.53.

  PMID: 12853784 BACKGROUND

• Thomas LD, Elinder CG, Tiselius HG, Wolk A, Akesson A. Ascorbic acid supplements and kidney stone incidence among men: a prospective study. JAMA Intern Med. 2013 Mar 11;173(5):386-8. doi: 10.1001/jamainternmed.2013.2296. No abstract available.

  PMID: 23381591 BACKGROUND

• Prier M, Carr AC, Baillie N. No Reported Renal Stones with Intravenous Vitamin C Administration: A Prospective Case Series Study. Antioxidants (Basel). 2018 May 21;7(5):68. doi: 10.3390/antiox7050068.

  PMID: 29883396 BACKGROUND

• Mitch WE, Johnson MW, Kirshenbaum JM, Lopez RE. Effect of large oral doses of ascorbic acid on uric acid excretion by normal subjects. Clin Pharmacol Ther. 1981 Mar;29(3):318-21. doi: 10.1038/clpt.1981.42.

  PMID: 7471601 BACKGROUND

• Auer BL, Auer D, Rodgers AL. The effect of ascorbic acid ingestion on the biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation. Clin Chem Lab Med. 1998 Mar;36(3):143-7. doi: 10.1515/CCLM.1998.027.

  PMID: 9589801 BACKGROUND

• Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3704-9. doi: 10.1073/pnas.93.8.3704.

  PMID: 8623000 BACKGROUND

• Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 2016 Sep;22(6):463-93. doi: 10.1111/odi.12446. Epub 2016 Apr 14.

  PMID: 26808119 BACKGROUND

• Zhang M, Jativa DF. Vitamin C supplementation in the critically ill: A systematic review and meta-analysis. SAGE Open Med. 2018 Oct 19;6:2050312118807615. doi: 10.1177/2050312118807615. eCollection 2018.

  PMID: 30364374 BACKGROUND

• Gerster H. No contribution of ascorbic acid to renal calcium oxalate stones. Ann Nutr Metab. 1997;41(5):269-82. doi: 10.1159/000177954.

  PMID: 9429689 BACKGROUND

• Zuckerman JD, Rokito A. Frozen shoulder: a consensus definition. J Shoulder Elbow Surg. 2011 Mar;20(2):322-5. doi: 10.1016/j.jse.2010.07.008. Epub 2010 Nov 4.

  PMID: 21051244 BACKGROUND

• Mejia-Hernandez K, Chang A, Eardley-Harris N, Jaarsma R, Gill TK, McLean JM. Smartphone applications for the evaluation of pathologic shoulder range of motion and shoulder scores-a comparative study. JSES Open Access. 2018 Mar 13;2(1):109-114. doi: 10.1016/j.jses.2017.10.001. eCollection 2018 Mar.

  PMID: 30675577 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Janine Antonov, Dr.

  Campus SLB, Lindenhof AG

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All study participants and trial personnel but the persons generating the randomization list and preparing the blinded drug packs at the Inselapotheke and Spitalapotheke Lindenhof will be blinded to the assigned treatment. Blinding will be upheld until all analyses are completed. Vitamin C and placebo will be provided in identical looking capsules in drug packs, which will also look identical except for the consecutive code number which is unique on each pack.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomly allocated to the two treatment arms, vitamin C or placebo, in a 1:1 ratio. The randomisation will be stratified by type of surgery performed. Allocation will be concealed using sequentially coded drug packs that are otherwise identical. Drug packs will be coded as 01-01 to 01-50 for stratum 1, 02-01 to 02-50 for stratum 2, 03-01 to 03-50 for stratum 3, and 04-01 to 04-50 for stratum 4. The 4 strata differ in the type of operation performed: 1. Rotator cuff surgery with resection of the acromioclavicular joint 2. Rotator cuff surgery without resection of the acromioclavicular joint 3. Shoulder arthroscopy with resection of the acromioclavicular joint 4. Shoulder arthroscopy without resection of the acromioclavicular joint Vitamin C will be administered orally at 1000 mg/day (500 mg b.i.d.) for 50 days post surgery.

Study Record Dates

• First Submitted: July 10, 2020
• First Posted: July 15, 2020
• Study Start: April 27, 2021
• Primary Completion: May 16, 2023
• Study Completion: April 21, 2024
• Last Updated: June 14, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)