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Milk Products in the Treatment of Hypophosphatemic Rickets

Primary Purpose

Hypophosphatemic Rickets

Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Phosphate tablets.
High cheese intake.
High milk intake.
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypophosphatemic Rickets

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Genetic verified hypophosphatemic rickets.
  • In treated with oral phosphate tablets.

Exclusion Criteria:

  • Tertiary hyperparathydoism.
  • In treatment with Cinacalcet.
  • Suffered from milk allergy.

Sites / Locations

  • Aarhus University Hospital, Skejby

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Phosphate tablets.

High cheese intake.

High milk intake.

Arm Description

800 mg oral phosphor supplement distributed over five times a day independently of any prior treatment dose.

Cheese with an estimated phosphate content of 800 mg distributed over 5 meals.

800 ml of milk daily corresponding to approximately 800 mg phosphor per day.

Outcomes

Primary Outcome Measures

Serum phosphate.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.

Secondary Outcome Measures

Fibroblast growth factor 23.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Parathyroid hormone.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Total calcium.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Basic phosphatase.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
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.
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.

Full Information

First Posted
October 9, 2017
Last Updated
November 15, 2017
Sponsor
University of Aarhus
Collaborators
University of East Anglia, Kolding Sygehus, Aarhus University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03348644
Brief Title
Milk Products in the Treatment of Hypophosphatemic Rickets
Official Title
Milk Products in the Treatment of Hypophosphatemic Rickets: A Randomised Crossover Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
August 1, 2015 (Actual)
Primary Completion Date
June 1, 2016 (Actual)
Study Completion Date
June 1, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
Collaborators
University of East Anglia, Kolding Sygehus, Aarhus University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypophosphatemic Rickets

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Randomized, multiple crossover study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phosphate tablets.
Arm Type
Experimental
Arm Description
800 mg oral phosphor supplement distributed over five times a day independently of any prior treatment dose.
Arm Title
High cheese intake.
Arm Type
Active Comparator
Arm Description
Cheese with an estimated phosphate content of 800 mg distributed over 5 meals.
Arm Title
High milk intake.
Arm Type
Active Comparator
Arm Description
800 ml of milk daily corresponding to approximately 800 mg phosphor per day.
Intervention Type
Dietary Supplement
Intervention Name(s)
Phosphate tablets.
Intervention Type
Dietary Supplement
Intervention Name(s)
High cheese intake.
Intervention Type
Dietary Supplement
Intervention Name(s)
High milk intake.
Primary Outcome Measure Information:
Title
Serum phosphate.
Description
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Time Frame
Three days.
Secondary Outcome Measure Information:
Title
Fibroblast growth factor 23.
Description
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Time Frame
Three days.
Title
Parathyroid hormone.
Description
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Time Frame
Three days.
Title
Total calcium.
Description
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Time Frame
Three days.
Title
Basic phosphatase.
Description
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Time Frame
Three days.
Title
Urine phosphate.
Description
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.
Time Frame
One day.
Title
Urine calcium.
Description
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.
Time Frame
One day.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Genetic verified hypophosphatemic rickets. In treated with oral phosphate tablets. Exclusion Criteria: Tertiary hyperparathydoism. In treatment with Cinacalcet. Suffered from milk allergy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Niels Birkebæk., MD, PhD
Organizational Affiliation
Aarhus University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital, Skejby
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Publication.
Citations:
PubMed Identifier
19095780
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.
Results Reference
background
PubMed Identifier
22695891
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.
Results Reference
background
PubMed Identifier
28703220
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.
Results Reference
background
PubMed Identifier
18365315
Citation
Bastepe M, Juppner 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.
Results Reference
background
PubMed Identifier
21538511
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. Erratum In: J Bone Miner Res. 2015 Feb;30(2):394.
Results Reference
background
PubMed Identifier
12419819
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. doi: 10.1074/jbc.M207872200. Epub 2002 Nov 4.
Results Reference
background
PubMed Identifier
16358214
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. doi: 10.1086/499409. Epub 2005 Dec 9.
Results Reference
background
PubMed Identifier
25123121
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.
Results Reference
background
PubMed Identifier
19837909
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.
Results Reference
background
PubMed Identifier
17401693
Citation
Karp HJ, Vaihia KP, Karkkainen MU, Niemisto 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. doi: 10.1007/s00223-007-9011-7. Epub 2007 Apr 1.
Results Reference
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Milk Products in the Treatment of Hypophosphatemic Rickets

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