Vitamin D3 in Sensory Recovery After Digital NERVe Suture (D3NERV). (D3NERV)

Vitamin D3 in Sensory Recovery After Digital NERVe Suture: a Randomized Controlled Trial.

Digital nerve injuries are frequent in a FESUM center (Federation Européenne des Services d'Urgences Mains), and they need to be repaired in order to reduce the risk of hypoesthesia and to prevent painful neuroma. Several animal studies have shown that Cholecalciferol improves axonal nerve regeneration and myelination. No study has ever been done on human subjects to evaluate the nerve regeneration after Cholecalciferol supplementation.

Our hypothesis is that Cholecalciferol supplementation could improve axonal nerve regeneration and myelination after traumatic digital nerve injuries treated by microsurgical sutures and reduce the risk of hypoesthesia and neuroma.

Study Overview

• Status: Recruiting
• Conditions: Digital Nerve Injury
• Intervention / Treatment: Drug: Cholecalciferol; Drug: Placebos

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Flore-Anne Lecoq, MD; Phone Number: +33251848884; Email: flore.lecoq@gmail.com

Study Locations

• France
  • Caen, France, 14000
    • Recruiting
    • Caen University Hospital
    • Contact: Parienti Jean-Jacques, PHD
  • Rouen, France, 76000
    • Recruiting
    • Rouen University Hospital
    • Contact: Auquit-Auckbur Isabelle, PHD
  • Saint-Herblain, France, 44800
    • Recruiting
    • Institut de la main Nantes Atlantique
    • Contact: Lecoq Flore-Anne, MD; Phone Number: 0251844884

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 47 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Affiliated to social security scheme,
• Wound of the palmar hand with isolated digital nerve section, requiring digital nerve microsurgical suture in the operating room by a senior surgeon,
• Signing a free and informed consent and well-informed of the study and procedure.

Exclusion Criteria:

• Ischemia,
• Multiple lesion of the same nerve,
• Pregnant or nursing women,
• Contraindication of Cholecalciferol : known hypersensitivity, any history of hypercalcemia, hypercalciuria or renal lithiasis,
• Cholecalciferol supplementation in the past 6 months,
• Lesion of the same controlateral finger,
• History of nerve lesion or hypoesthesia on the same finger,
• History of previous neurological disorders with upper limb sensitivity disorder,
• Impossibility to undergo the medical follow-up because of geographical, social or psychological reason,
• Participation in another clinical trial that does not allow simultaneous participation in several clinical trials,
• Orlistat® Treatment,
• History of celiac disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cholecalciferol; Cholecalciferol (Vitamin D3) 100 000 IU/2 mL	Drug: Cholecalciferol; One vial every 15 days during 2 months
Placebo Comparator: Placebo; Placebo of Cholecalciferol (Vitamine D3) 100 000 IU/2 mL	Drug: Placebos; One vial every 15 days during 2 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weber test (Month 6)	2 point discrimination test of Weber on the side of the fingertip concerned by the wound, comparing to the controlateral arm, after 6 months.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weber test (Month 12)	2 point discrimination test of Weber on the side of the fingertip concerned by the wound, comparing to the controlateral arm, after 12 months.	Month 12
Resting pain on the operated finger	VAS (Visual Analogic Scale)	Month 2, Month 6, Month 12
Neuropathic pain on the operated finger	DN 4 (Neuropathic pain)	Month 2, Month 6, Month 12
Global functional outcome measure	Quick DASH	Month 2, Month 6, Month 12
Cold Intolerance	CSS (Cold Sensitivity Severity Scale)	Month 2, Month 6, Month 12
Cold Intolerance at work	PWES (Potential Work Exposure Scale)	Month 2, Month 6, Month 12
Quality-of-life measure	SF-36 (Study Short form 36)	Month 2, Month 6, Month 12
Return-to-work time frames	Time before returning to work	Month 2
Vitamin D blood level		at inclusion, Month 2
Adverse event and complication	Existence of neuroma, existence of medical complication, existence of overdosage of Cholecalciferol and every other adverse event	Trough study completion

Collaborators and Investigators

• Sponsor: University Hospital, Caen

Publications and helpful links

General Publications

• Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. doi: 10.1093/ajcn/69.5.842.
• Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001 Feb;73(2):288-94. doi: 10.1093/ajcn/73.2.288.
• Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003 Jan;77(1):204-10. doi: 10.1093/ajcn/77.1.204. Erratum In: Am J Clin Nutr. 2003 Nov;78(5):1047.
• al-Ghazal SK, McKiernan M, Khan K, McCann J. Results of clinical assessment after primary digital nerve repair. J Hand Surg Br. 1994 Apr;19(2):255-7. doi: 10.1016/0266-7681(94)90180-5.
• Alligand-Perrin P, Rabarin F, Jeudy J, Cesari B, Saint-Cast Y, Fouque PA, Raimbeau G. Vein conduit associated with microsurgical suture for complete collateral digital nerve severance. Orthop Traumatol Surg Res. 2011 Jun;97(4 Suppl):S16-20. doi: 10.1016/j.otsr.2011.03.012. Epub 2011 Apr 30.
• Arnaout A, Fontaine C, Chantelot C. Sensory recovery after primary repair of palmar digital nerves using a Revolnerv((R)) collagen conduit: a prospective series of 27 cases. Chir Main. 2014 Sep;33(4):279-85. doi: 10.1016/j.main.2014.05.002. Epub 2014 Jun 18.
• Barrueto F Jr, Wang-Flores HH, Howland MA, Hoffman RS, Nelson LS. Acute vitamin D intoxication in a child. Pediatrics. 2005 Sep;116(3):e453-6. doi: 10.1542/peds.2004-2580.
• Battiston B, Geuna S, Ferrero M, Tos P. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery. 2005;25(4):258-67. doi: 10.1002/micr.20127.
• Bertleff MJ, Meek MF, Nicolai JP. A prospective clinical evaluation of biodegradable neurolac nerve guides for sensory nerve repair in the hand. J Hand Surg Am. 2005 May;30(3):513-8. doi: 10.1016/j.jhsa.2004.12.009.
• Chabas JF, Stephan D, Marqueste T, Garcia S, Lavaut MN, Nguyen C, Legre R, Khrestchatisky M, Decherchi P, Feron F. Cholecalciferol (vitamin D(3)) improves myelination and recovery after nerve injury. PLoS One. 2013 May 31;8(5):e65034. doi: 10.1371/journal.pone.0065034. Print 2013.
• Neubrech F, Heider S, Otte M, Hirche C, Kneser U, Kremer T. [Nerve Tubes for the Repair of Traumatic Sensory Nerve Lesions of the Hand: Review and Planning Study for a Randomised Controlled Multicentre Trial]. Handchir Mikrochir Plast Chir. 2016 Jun;48(3):148-54. doi: 10.1055/s-0042-104505. Epub 2016 Jun 16. German.
• Finnell JT, Knopp R, Johnson P, Holland PC, Schubert W. A calibrated paper clip is a reliable measure of two-point discrimination. Acad Emerg Med. 2004 Jun;11(6):710-4.
• Gueye Y, Marqueste T, Maurel F, Khrestchatisky M, Decherchi P, Feron F. Cholecalciferol (vitamin D(3)) improves functional recovery when delivered during the acute phase after a spinal cord trauma. J Steroid Biochem Mol Biol. 2015 Nov;154:23-31. doi: 10.1016/j.jsbmb.2015.06.007. Epub 2015 Jul 6.
• Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab. 2002 Nov;87(11):4952-6. doi: 10.1210/jc.2002-020636.
• Lundborg G, Rosen B. The two-point discrimination test--time for a re-appraisal? J Hand Surg Br. 2004 Oct;29(5):418-22. doi: 10.1016/j.jhsb.2004.02.008.
• Fakin RM, Calcagni M, Klein HJ, Giovanoli P. Long-term clinical outcome after epineural coaptation of digital nerves. J Hand Surg Eur Vol. 2016 Feb;41(2):148-54. doi: 10.1177/1753193415578986. Epub 2015 Mar 31.
• Manoli T, Schiefer JL, Schulz L, Fuchsberger T, Schaller HE. Influence of immobilization and sensory re-education on the sensory recovery after reconstruction of digital nerves with direct suture or muscle-in-vein conduits. Neural Regen Res. 2016 Feb;11(2):338-44. doi: 10.4103/1673-5374.169638.
• Montava M, Garcia S, Mancini J, Jammes Y, Courageot J, Lavieille JP, Feron F. Vitamin D3 potentiates myelination and recovery after facial nerve injury. Eur Arch Otorhinolaryngol. 2015 Oct;272(10):2815-23. doi: 10.1007/s00405-014-3305-y. Epub 2014 Sep 27.
• Pomares G, Dap F, Dautel G. Complete section of proper palmar digital pedicles: Correlation between arterial patency and sensory recovery. Hand Surg Rehabil. 2017 Apr;36(2):136-140. doi: 10.1016/j.hansur.2016.12.001. Epub 2017 Mar 9.
• Przybelski R, Agrawal S, Krueger D, Engelke JA, Walbrun F, Binkley N. Rapid correction of low vitamin D status in nursing home residents. Osteoporos Int. 2008 Nov;19(11):1621-8. doi: 10.1007/s00198-008-0619-x. Epub 2008 Apr 18.
• Romagnoli E, Mascia ML, Cipriani C, Fassino V, Mazzei F, D'Erasmo E, Carnevale V, Scillitani A, Minisola S. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab. 2008 Aug;93(8):3015-20. doi: 10.1210/jc.2008-0350. Epub 2008 May 20.
• Shimokata H, Kuzuya F. Two-point discrimination test of the skin as an index of sensory aging. Gerontology. 1995;41(5):267-72. doi: 10.1159/000213693.
• Shooter D. Use of two-point discrimination as a nerve repair assessment tool: preliminary report. ANZ J Surg. 2005 Oct;75(10):866-8. doi: 10.1111/j.1445-2197.2005.03557.x.
• Taylor PN, Davies JS. A review of the growing risk of vitamin D toxicity from inappropriate practice. Br J Clin Pharmacol. 2018 Jun;84(6):1121-1127. doi: 10.1111/bcp.13573. Epub 2018 Apr 16.
• Vieth R. Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):575-9. doi: 10.1016/j.jsbmb.2004.03.038.
• Vieth R, Pinto TR, Reen BS, Wong MM. Vitamin D poisoning by table sugar. Lancet. 2002 Feb 23;359(9307):672. doi: 10.1016/S0140-6736(02)07814-5. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: October 3, 2019
• First Posted (Actual): October 4, 2019

Study Record Updates

• Last Update Posted (Actual): August 31, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: cholecalciferol; digital nerve injury; neuroma
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 17-237; 2018-001526-26 (EudraCT Number)

Drug and device information, study documents

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