Milk Products in the Treatment of Hypophosphatemic Rickets

Hypophosphatemic Rickets Clinical Trial

Official title:

Milk Products in the Treatment of Hypophosphatemic Rickets: A Randomised Crossover Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03348644
• Other study ID #: Milk products in HPR
• Status: Completed
• Phase: N/A
• First received: October 9, 2017
• Last updated: November 15, 2017
• Start date: August 1, 2015
• Est. completion date: June 1, 2016

Study information

• Verified date: October 2017
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study was to investigate the feasibility and efficacy of a high intake of milk and/or cheese products compared to phosphate tablets in patients with hypophosphatemic rickets when evaluating the S-phosphate levels as a main effect parameter. The study was designed as a randomized, multiple crossover study.

Description:

Objectives:

Standard treatment of hypophosphatemic rickets consists of oral phosphate tablets and vitamin D analogous. Due to their rapid absorption, serum-phosphate fluctuations can occur and secondary hyperparathyroidism may be a consequence. Our aim was to evaluate, if phosphate supplement administered as milk or cheese is superior or equal to phosphate tablets in patients with hypophosphatemic rickets

Study population:

Patients with genetic verified hypophosphatemic rickets were included in the period from August 2015 to June 2016. Patients were excluded from the study if they presented with tertiary hyperparathydoism, were treated with Cinacalcet or suffered from milk allergy.

Study design:

The study was designed as a randomized, multiple crossover study with three treatment periods consisting of the regular oral phosphate supplement, a high milk intake or a high cheese intake (randomization.com). Patients were instructed to discontinue their regular treatment, except for their usual doses of D vitamin analogs, three days prior to sample collection and instead engage in the study treatment. Furthermore, they should follow their normal eating habits while undergoing the study treatment, which was controlled by food and liquid registrations.

At the phosphate supplement session, the patients were treated with an 800 mg oral phosphor supplement distributed over five times a day independently of any prior treatment dose. At the cheese session, the patients were treated with an estimated phosphate content of 800 mg distributed over 5 meals. At the milk session, the patients were treated with 800 ml of milk daily corresponding to approximately 800 mg phosphor per day.

Sampling:

After three days of treatment, the patients visited our clinic for anaerobically handled blood samples, which were collected 5 times through out one day for calcium, phosphate, parathyroid hormone, fibroblast growth factor 23 and basic phosphatase. Urine samples for calcium and phosphate was collected in containers from 0800 to 1200 and from 1200 to 1600. A 24-hour urine samples was obtained from the day before the sampling from 0800 to 0800 hours the following morning.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: June 1, 2016
• Est. primary completion date: June 1, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years and older

Eligibility

Inclusion Criteria:

• Genetic verified hypophosphatemic rickets.

• In treated with oral phosphate tablets.

Exclusion Criteria:

• Tertiary hyperparathydoism.

• In treatment with Cinacalcet.

• Suffered from milk allergy.

Related Conditions & MeSH terms

• Familial Hypophosphatemic Rickets
• Hypophosphatemic Rickets
• Rickets

Intervention

Dietary Supplement:
• Phosphate tablets.

• High cheese intake.

• High milk intake.

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, Skejby	Aarhus N

Sponsors (4)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Kolding Sygehus, University of East Anglia

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

Bastepe M, Jüppner H. Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation. Rev Endocr Metab Disord. 2008 Jun;9(2):171-80. doi: 10.1007/s11154-008-9075-3. Epub 2008 Mar 26. Review. — View Citation

Beck-Nielsen SS, Brixen K, Gram J, Brusgaard K. Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets. J Hum Genet. 2012 Jul;57(7):453-8. doi: 10.1038/jhg.2012.56. Epub 2012 Jun 14. — View Citation

Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK. Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol. 2009 Mar;160(3):491-7. doi: 10.1530/EJE-08-0818. Epub 2008 Dec 18. — View Citation

Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H. SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet. 2006 Feb;78(2):179-92. Epub 2005 Dec 9. — View Citation

Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res. 2011 Jul;26(7):1381-8. doi: 10.1002/jbmr.340. Epub 2011 May 2. Review. Erratum in: J Bone Miner Res. 2015 Feb;30(2):394. — View Citation

Karp HJ, Vaihia KP, Kärkkäinen MU, Niemistö MJ, Lamberg-Allardt CJ. Acute effects of different phosphorus sources on calcium and bone metabolism in young women: a whole-foods approach. Calcif Tissue Int. 2007 Apr;80(4):251-8. Epub 2007 Apr 1. — View Citation

Minisola S, Peacock M, Fukumoto S, Cipriani C, Pepe J, Tella SH, Collins MT. Tumour-induced osteomalacia. Nat Rev Dis Primers. 2017 Jul 13;3:17044. doi: 10.1038/nrdp.2017.44. Review. — View Citation

Nielsen LH, Rahbek ET, Beck-Nielsen SS, Christesen HT. Treatment of hypophosphataemic rickets in children remains a challenge. Dan Med J. 2014 Jul;61(7):A4874. — View Citation

Peacock M, Bolognese MA, Borofsky M, Scumpia S, Sterling LR, Cheng S, Shoback D. Cinacalcet treatment of primary hyperparathyroidism: biochemical and bone densitometric outcomes in a five-year study. J Clin Endocrinol Metab. 2009 Dec;94(12):4860-7. doi: 10.1210/jc.2009-1472. Epub 2009 Oct 16. — View Citation

Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N. Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. J Biol Chem. 2003 Jan 24;278(4):2206-11. Epub 2002 Nov 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum phosphate.	Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.	Three days.
Secondary	Fibroblast growth factor 23.	Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.	Three days.
Secondary	Parathyroid hormone.	Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.	Three days.
Secondary	Total calcium.	Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.	Three days.
Secondary	Basic phosphatase.	Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.	Three days.
Secondary	Urine phosphate.	Evaluated in urine samples. Urine samples for phosphate was collected in containers from 0800 to 1200 and from 1200 to 1600. A 24-hour urine samples was obtained from the day before the sampling from 0800 to 0800 hours the following morning.	One day.
Secondary	Urine calcium.	Evaluated in urine samples. Urine samples for calcium was collected in containers from 0800 to 1200 and from 1200 to 1600. A 24-hour urine samples was obtained from the day before the sampling from 0800 to 0800 hours the following morning.	One day.