Pilot Study: The Effect of Ergocalciferol on Plasma Mucin-1 Levels

Ergocalciferol Clinical Trial

Official title:

Study of the Effect of Ergocalciferol on Plasma and Urinary Mucin-1 Levels in Healthy Individuals and Individuals With Autosomal Dominant Tubulo-Interstitial Kidney Disease Due to MUC1 Mutations (ADTKD-MUC1)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03747523
• Other study ID #: IRB00054784
• Status: Completed
• Phase: Early Phase 1
• Start date: March 12, 2019
• Est. completion date: January 27, 2020

Study information

• Verified date: January 2020
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine if a one-time oral administration of ergocalciferol results in a decline in plasma mucin-1 levels in healthy individuals and individuals with ADTKD-MUC1.

Description:

This is a pilot, open-labelled, to determine if oral administration of a single dose of ergocalciferol lowers plasma mucin-1 levels. The study population will include 40 healthy individuals and 40 individuals with ADTKD-MUC1.

The study consists of an initial screening, signing of consent of interested individuals, performance of pregnancy test in women of child-bearing age and screening labs, and administration of 200,000 units of ergocalciferol on Day 0 (On Study). Laboratory studies will be performed at baseline, on Days 3, 7, and 10.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 27, 2020
• Est. primary completion date: December 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age > 18 years and <65 years

• Females must be non-pregnant, non-lactating and fulfilling one of the following: a. Post menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments. b. Status post irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. c.

Use of acceptable contraceptive method: IUD with spermicide, a female condom with spermicide, contraceptive sponge with spermicide, an intravaginal system(e.g., NuvaRing®), a diaphragm with spermicide, a cervical cap with spermicide, or oral, implantable, transdermal, or injectable contraceptives, sexual abstinence, or a sterile sexual partner.

• Males must agree to avoid fathering a child (or donating sperm), and therefore be either sterile or agree to use, from the time of enrollment until 45 days after end of study, one of the following approved methods of contraception: a male condom with spermicide, a sterile sexual partner, use by female sexual partner of an IUD with spermicide, a female condom with spermicide, contraceptive sponge with spermicide, an intravaginal system (e.g.,NuvaRing®), a diaphragm with spermicide, a cervical cap with spermicide, or oral, implantable, transdermal, or injectable contraceptives.

• No serious health conditions except for estimated glomerular filtration rate <30 ml/min/1.73 m2 (according to the modified MDRD formula) in participants with ADTKD- MUC1.

• Prior established genetic diagnosis of ADTKD-MUC1 in participants recruited with ADTKD-MUC1.

• Able to understand and comply with requirements of the entire study and to communicate with the study team.

• Living in close enough proximity to a local laboratory to obtain labwork for the study.

• Written informed consent using a document that has been approved by the Institutional Review Board.

• The participant has not taken ergocalciferol in the month prior to study initiation. If receiving cholecalciferol, the dose is < 1000/day and has been stopped one month prior to Day 0 (On Study).

• Participants agree NOT to take ergocalciferol or cholecalciferol (except for<500 IU that contained in a daily multi-vitamin) for six months after receiving the one-time dose of ergocalciferol.

Exclusion Criteria:

• Major systemic illness other than chronic kidney disease in individuals with ADTKD- MUC1.

• A history of granulomatous disorders (sarcoidosis, tuberculosis), hyperparathyroidism, or other disorders of calcium metabolism.

• A history of nephrolithiasis.

• A history of osteoporosis or osteopenia.

• A fracture or a fall that did not occur during exercise within the last six months.

• Intolerance or known allergic reaction to ergocalciferol.

• 25 hydroxy Vitamin D level > upper limit of normal.

• Lactating.

• Liver disease.

• Receiving glucocorticoids.

Related Conditions & MeSH terms

• Ergocalciferol

Intervention

Drug:
• Ergocalciferol
Investigational drug will be administered to eligible participants in a single dose of 200,000 USP units vitamin D

Locations

Country	Name	City	State
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (40)

Živná M, Kidd K, Pristoupilová A, Barešová V, DeFelice M, Blumenstiel B, Harden M, Conlon P, Lavin P, Connaughton DM, Hartmannová H, Hodanová K, Stránecký V, Vrbacká A, Vyletal P, Živný J, Votruba M, Sovová J, Hulková H, Robins V, Perry R, Wenzel A, Beck BB, Seeman T, Viklický O, Rajnochová-Bloudícková S, Papagregoriou G, Deltas CC, Alper SL, Greka A, Bleyer AJ, Kmoch S. Noninvasive Immunohistochemical Diagnosis and Novel MUC1 Mutations Causing Autosomal Dominant Tubulointerstitial Kidney Disease. J Am Soc Nephrol. 2018 Sep;29(9):2418-2431. doi: 10.1681/ASN.2018020180. Epub 2018 Jul 2. Erratum in: J Am Soc Nephrol. 2020 Apr;31(4):892. — View Citation

Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH, Stojakovic T, Schnedl C, Dobnig H. Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized, double-blind, placebo-controlled pilot study. Crit Care. 2011;15(2):R104. doi: 10.1186/cc10120. Epub 2011 Mar 28. — View Citation

Apostolopoulos V, Stojanovska L, Gargosky SE. MUC1 (CD227): a multi-tasked molecule. Cell Mol Life Sci. 2015 Dec;72(23):4475-500. doi: 10.1007/s00018-015-2014-z. Epub 2015 Aug 21. Review. — View Citation

Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. — View Citation

Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. High-dose oral vitamin D3 supplementation in the elderly. Osteoporos Int. 2009 Aug;20(8):1407-15. doi: 10.1007/s00198-008-0814-9. Epub 2008 Dec 20. — View Citation

Bleyer AJ, Kmoch S, Antignac C, Robins V, Kidd K, Kelsoe JR, Hladik G, Klemmer P, Knohl SJ, Scheinman SJ, Vo N, Santi A, Harris A, Canaday O, Weller N, Hulick PJ, Vogel K, Rahbari-Oskoui FF, Tuazon J, Deltas C, Somers D, Megarbane A, Kimmel PL, Sperati CJ, Orr-Urtreger A, Ben-Shachar S, Waugh DA, McGinn S, Bleyer AJ Jr, Hodanová K, Vylet'al P, Živná M, Hart TC, Hart PS. Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1. Clin J Am Soc Nephrol. 2014 Mar;9(3):527-35. doi: 10.2215/CJN.06380613. Epub 2014 Feb 7. — View Citation

Bleyer AJ, Kmoch S: Autosomal Dominant Tubulointerstitial Kidney Disease, MUC1-Related. 1993

Bonella F, Long X, Ohshimo S, Horimasu Y, Griese M, Guzman J, Kohno N, Costabel U. MUC1 gene polymorphisms are associated with serum KL-6 levels and pulmonary dysfunction in pulmonary alveolar proteinosis. Orphanet J Rare Dis. 2016 Apr 23;11:48. doi: 10.1186/s13023-016-0430-2. — View Citation

Conley SJ, Bosco EE, Tice DA, Hollingsworth RE, Herbst R, Xiao Z. HER2 drives Mucin-like 1 to control proliferation in breast cancer cells. Oncogene. 2016 Aug 11;35(32):4225-34. doi: 10.1038/onc.2015.487. Epub 2016 Jan 4. — View Citation

Corsello SM, Bittker JA, Liu Z, Gould J, McCarren P, Hirschman JE, Johnston SE, Vrcic A, Wong B, Khan M, Asiedu J, Narayan R, Mader CC, Subramanian A, Golub TR. The Drug Repurposing Hub: a next-generation drug library and information resource. Nat Med. 2017 Apr 7;23(4):405-408. doi: 10.1038/nm.4306. — View Citation

Estébanez N, Gómez-Acebo I, Palazuelos C, Llorca J, Dierssen-Sotos T. Vitamin D exposure and Risk of Breast Cancer: a meta-analysis. Sci Rep. 2018 Jun 13;8(1):9039. doi: 10.1038/s41598-018-27297-1. — View Citation

Grossmann RE, Zughaier SM, Kumari M, Seydafkan S, Lyles RH, Liu S, Sueblinvong V, Schechter MS, Stecenko AA, Ziegler TR, Tangpricha V. Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial. Dermatoendocrinol. 2012 Apr 1;4(2):191-7. doi: 10.4161/derm.20332. — View Citation

Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW. 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under various input conditions. Am J Clin Nutr. 2008 Jun;87(6):1738-42. — View Citation

Horimasu Y, Hattori N, Ishikawa N, Kawase S, Tanaka S, Yoshioka K, Yokoyama A, Kohno N, Bonella F, Guzman J, Ohshimo S, Costabel U. Different MUC1 gene polymorphisms in German and Japanese ethnicities affect serum KL-6 levels. Respir Med. 2012 Dec;106(12):1756-64. doi: 10.1016/j.rmed.2012.09.001. Epub 2012 Sep 18. — View Citation

Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006 Oct;84(4):694-7. — View Citation

Janssen R, Kruit A, Grutters JC, Ruven HJ, Gerritsen WB, van den Bosch JM. The mucin-1 568 adenosine to guanine polymorphism influences serum Krebs von den Lungen-6 levels. Am J Respir Cell Mol Biol. 2006 Apr;34(4):496-9. Epub 2005 Dec 15. — View Citation

Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008 Aug;88(2):582S-586S. Review. — View Citation

Kearns MD, Alvarez JA, Tangpricha V. Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review. Endocr Pract. 2014 Apr;20(4):341-51. doi: 10.4158/EP13265.RA. Review. — View Citation

Kearns MD, Binongo JN, Watson D, Alvarez JA, Lodin D, Ziegler TR, Tangpricha V. The effect of a single, large bolus of vitamin D in healthy adults over the winter and following year: a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. 2015 Feb;69(2):193-7. doi: 10.1038/ejcn.2014.209. Epub 2014 Oct 1. — View Citation

Kirby A, Gnirke A, Jaffe DB, Barešová V, Pochet N, Blumenstiel B, Ye C, Aird D, Stevens C, Robinson JT, Cabili MN, Gat-Viks I, Kelliher E, Daza R, DeFelice M, Hulková H, Sovová J, Vylet'al P, Antignac C, Guttman M, Handsaker RE, Perrin D, Steelman S, Sigurdsson S, Scheinman SJ, Sougnez C, Cibulskis K, Parkin M, Green T, Rossin E, Zody MC, Xavier RJ, Pollak MR, Alper SL, Lindblad-Toh K, Gabriel S, Hart PS, Regev A, Nusbaum C, Kmoch S, Bleyer AJ, Lander ES, Daly MJ. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat Genet. 2013 Mar;45(3):299-303. doi: 10.1038/ng.2543. Epub 2013 Feb 10. — View Citation

Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID; Fitness Collaborative Group. A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). J Am Geriatr Soc. 2003 Mar;51(3):291-9. — View Citation

Lee JP, Tansey M, Jetton JG, Krasowski MD. Vitamin D Toxicity: A 16-Year Retrospective Study at an Academic Medical Center. Lab Med. 2018 Mar 21;49(2):123-129. doi: 10.1093/labmed/lmx077. — View Citation

Leventis P, Kiely PD. The tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency. Scand J Rheumatol. 2009 Mar-Apr;38(2):149-53. doi: 10.1080/03009740802419081. — View Citation

Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16;130(6):461-70. — View Citation

Ligtenberg MJ, Gennissen AM, Vos HL, Hilkens J. A single nucleotide polymorphism in an exon dictates allele dependent differential splicing of episialin mRNA. Nucleic Acids Res. 1991 Jan 25;19(2):297-301. — View Citation

Logan VF, Gray AR, Peddie MC, Harper MJ, Houghton LA. Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. Br J Nutr. 2013 Mar 28;109(6):1082-8. doi: 10.1017/S0007114512002851. Epub 2012 Jul 11. — View Citation

Nguyen B, Venet D, Azim HA Jr, Brown D, Desmedt C, Lambertini M, Majjaj S, Pruneri G, Peccatori F, Piccart M, Rothé F, Sotiriou C. Breast cancer diagnosed during pregnancy is associated with enrichment of non-silent mutations, mismatch repair deficiency signature and mucin mutations. NPJ Breast Cancer. 2018 Aug 6;4:23. doi: 10.1038/s41523-018-0077-3. eCollection 2018. — View Citation

Premaor MO, Scalco R, da Silva MJ, Froehlich PE, Furlanetto TW. The effect of a single dose versus a daily dose of cholecalciferol on the serum 25-hydroxycholecalciferol and parathyroid hormone levels in the elderly with secondary hyperparathyroidism living in a low-income housing unit. J Bone Miner Metab. 2008;26(6):603-8. doi: 10.1007/s00774-008-0858-0. Epub 2008 Nov 1. — View Citation

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. — View Citation

Rossini M, Gatti D, Viapiana O, Fracassi E, Idolazzi L, Zanoni S, Adami S. Short-term effects on bone turnover markers of a single high dose of oral vitamin D3. J Clin Endocrinol Metab. 2012 Apr;97(4):E622-6. doi: 10.1210/jc.2011-2448. Epub 2012 Feb 1. — View Citation

Sakalli H, Arslan D, Yucel AE. The effect of oral and parenteral vitamin D supplementation in the elderly: a prospective, double-blinded, randomized, placebo-controlled study. Rheumatol Int. 2012 Aug;32(8):2279-83. doi: 10.1007/s00296-011-1943-6. Epub 2011 May 10. — View Citation

Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010 May 12;303(18):1815-22. doi: 10.1001/jama.2010.594. Erratum in: JAMA. 2010 Jun 16;303(23):2357. — View Citation

Sinn BV, von Minckwitz G, Denkert C, Eidtmann H, Darb-Esfahani S, Tesch H, Kronenwett R, Hoffmann G, Belau A, Thommsen C, Holzhausen HJ, Grasshoff ST, Baumann K, Mehta K, Dietel M, Loibl S. Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer. Ann Oncol. 2013 Sep;24(9):2316-24. doi: 10.1093/annonc/mdt162. Epub 2013 May 9. — View Citation

Smith H, Anderson F, Raphael H, Maslin P, Crozier S, Cooper C. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women--a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford). 2007 Dec;46(12):1852-7. Epub 2007 Nov 12. — View Citation

Spicer AP, Rowse GJ, Lidner TK, Gendler SJ. Delayed mammary tumor progression in Muc-1 null mice. J Biol Chem. 1995 Dec 15;270(50):30093-101. — View Citation

Stoll D, Dudler J, Lamy O, Hans D, Krieg MA, Aubry-Rozier B. Can one or two high doses of oral vitamin D3 correct insufficiency in a non-supplemented rheumatologic population? Osteoporos Int. 2013 Feb;24(2):495-500. doi: 10.1007/s00198-012-1962-5. Epub 2012 Mar 17. — View Citation

Tellioglu A, Basaran S, Guzel R, Seydaoglu G. Efficacy and safety of high dose intramuscular or oral cholecalciferol in vitamin D deficient/insufficient elderly. Maturitas. 2012 Aug;72(4):332-8. doi: 10.1016/j.maturitas.2012.04.011. Epub 2012 May 20. — View Citation

Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998 Oct;68(4):854-8. — View Citation

Witham MD, Dove FJ, Dryburgh M, Sugden JA, Morris AD, Struthers AD. The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial. Diabetologia. 2010 Oct;53(10):2112-9. doi: 10.1007/s00125-010-1838-1. Epub 2010 Jul 2. — View Citation

Yu CK, Sykes L, Sethi M, Teoh TG, Robinson S. Vitamin D deficiency and supplementation during pregnancy. Clin Endocrinol (Oxf). 2009 May;70(5):685-90. doi: 10.1111/j.1365-2265.2008.03403.x. Epub 2008 Sep 2. — View Citation

* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma mucin-1 levels	Plasma mucin-1 levels will be measured in both groups. using a two-tailed T-test.	Baseline
Primary	Plasma mucin-1 levels	Plasma mucin-1 levels will be measured in both groups. using a two-tailed T-test.	3 days
Secondary	Plasma mucin-1 levels	Plasma mucin-1 levels will be measured in will be measured in both groups.	7 days
Secondary	Plasma mucin-1 levels	Plasma mucin-1 levels will be measured in will be measured in both groups.	10 days
Secondary	Urinary mucin-1 levels in healthy controls	Urinary mucin-1 levels	Baseline
Secondary	Urinary mucin-1 levels in healthy controls	Urinary mucin-1 levels	3 days
Secondary	Urinary mucin-1 levels in healthy controls	Urinary mucin-1 levels	7 days
Secondary	Urinary mucin-1 levels in healthy controls	Urinary mucin-1 levels	10 days