Milk Products in the Treatment of Hypophosphatemic Rickets

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Hypophosphatemic Rickets

Intervention / Treatment
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* Dietary Supplement: Phosphate tablets.
* Dietary Supplement: High cheese intake.
* Dietary Supplement: High milk intake.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genetic verified hypophosphatemic rickets. In treated with oral phosphate tablets. Exclusion Criteria: Tertiary hyperparathydoism. In treatment with Cinacalcet. Suffered from milk allergy.

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, multiple crossover study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phosphate tablets.<br>800 mg oral phosphor supplement distributed over five times a day independently of any prior treatment dose. | Dietary Supplement: Phosphate tablets.<br> <br> |
| Active Comparator: High cheese intake.<br>Cheese with an estimated phosphate content of 800 mg distributed over 5 meals. | Dietary Supplement: High cheese intake.<br> <br> |
| Active Comparator: High milk intake.<br>800 ml of milk daily corresponding to approximately 800 mg phosphor per day. | Dietary Supplement: High milk intake.<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| Parathyroid hormone. | Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day. | Three days. | 
| Total calcium. | Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day. | Three days. | 
| Basic phosphatase. | Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day. | Three days. | 
| 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. | 
| 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. |