Hypophosphatemic RicketsNCT03348644
Milk Products in the Treatment of Hypophosphatemic Rickets
A study testing Phosphate tablets., High cheese intake. and High milk intake. in people with Hypophosphatemic Rickets, run by University of Aarhus at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 14 years and older, women only
- Conditions the study is for
- Hypophosphatemic Rickets
- What is being tested?
- Phosphate tablets., High cheese intake. and High milk intake.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Aug 2015to 1 Jun 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Genetic verified hypophosphatemic rickets.
- In treated with oral phosphate tablets.
Who cannot join
- Tertiary hyperparathydoism.
- In treatment with Cinacalcet.
- Suffered from milk allergy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Milk Products in the Treatment of Hypophosphatemic Rickets: A Randomised Crossover Trial
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.
Read the 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.
- Conditions
- Hypophosphatemic Rickets
- Being tested
- Phosphate tablets., High cheese intake., High milk intake.
- Medical subject headings
- Rickets, Hypophosphatemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phosphate tablets.Dietary supplement
High cheese intake.Dietary supplement
High milk intake.Dietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Phosphate tablets. | Experimental | 800 mg oral phosphor supplement distributed over five times a day independently of any prior treatment dose. Receives: Dietary Supplement: Phosphate tablets. |
| High cheese intake. | Active comparator | Cheese with an estimated phosphate content of 800 mg distributed over 5 meals. Receives: Dietary Supplement: High cheese intake. |
| High milk intake. | Active comparator | 800 ml of milk daily corresponding to approximately 800 mg phosphor per day. Receives: Dietary Supplement: High milk intake. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum phosphate.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Measured: Three days.
Secondary outcomes (6)
Fibroblast growth factor 23.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Measured: Three days.
Parathyroid hormone.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Measured: Three days.
Total calcium.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Measured: Three days.
Basic phosphatase.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
Measured: 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.
Measured: 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.
Measured: One day.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2017
- Study start1 Aug 2015
- Primary completion1 Jun 2016
- Study completion1 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Hypophosphatemic RicketsStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, multiple crossover study
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- University of East Anglia, Kolding Sygehus, Aarhus University Hospital
- Responsible party
- Sponsor
- Investigators
- Niels Birkebæk., MD, PhD, Principal investigator, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03348644
- Sponsor's protocol ID
- Milk products in HPR
- Status last verified
- Oct 2017
- First submitted
- 9 Oct 2017
- Last updated
- 21 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Publication.
Publications
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.
PubMed 19095780Beck-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.
PubMed 22695891Minisola 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.
PubMed 28703220Bastepe 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.
PubMed 18365315Carpenter 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.
PubMed 21538511Saito 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.
PubMed 12419819Bergwitz 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.
PubMed 16358214Nielsen 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.
PubMed 25123121Peacock 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.
PubMed 19837909Karp 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.
PubMed 17401693
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Milk Products in the Treatment of Hypophosphatemic Rickets: A Randomised Crossover Trial
- ClinicalTrials.gov ID
- NCT03348644
- Acronym / sponsor ID
- Milk products in HPR
- Conditions
- Hypophosphatemic Rickets
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- University of East Anglia, Kolding Sygehus, Aarhus University Hospital
- Study start
- 1 Aug 2015 (actual)
- Primary completion
- 1 Jun 2016 (actual)
- Study completion
- 1 Jun 2016 (actual)
- First posted
- 21 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Randomized, multiple crossover study
| Arm | Type | Receives |
|---|---|---|
| Phosphate tablets. | Experimental | Dietary Supplement: Phosphate tablets.800 mg oral phosphor supplement distributed over five times a day independently of any prior treatment dose. |
| High cheese intake. | Active comparator | Dietary Supplement: High cheese intake.Cheese with an estimated phosphate content of 800 mg distributed over 5 meals. |
| High milk intake. | Active comparator | Dietary Supplement: High milk intake.800 ml of milk daily corresponding to approximately 800 mg phosphor per day. |
Who may qualify
- Ages
- 14 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Genetic verified hypophosphatemic rickets.
- In treated with oral phosphate tablets.
Key exclusion criteria (3 listed)
- Tertiary hyperparathydoism.
- In treatment with Cinacalcet.
- Suffered from milk allergy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phosphate tablets. | Dietary supplement | Phosphate tablets. |
| High cheese intake. | Dietary supplement | High cheese intake. |
| High milk intake. | Dietary supplement | High milk intake. |
Primary outcome
Serum phosphate.
Time frame: Three days.
Evaluated in blood samples. Evaluated after three days of treatment, where we collected blood 5 times through out one day.
6 secondary outcomes
Fibroblast growth factor 23.
Time frame: Three days.
Parathyroid hormone.
Time frame: Three days.
Total calcium.
Time frame: Three days.
Basic phosphatase.
Time frame: Three days.
Urine phosphate.
Time frame: One day.
Urine calcium.
Time frame: One day.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2017.
- Background: PubMed 19095780Beck-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.
- Background: PubMed 22695891Beck-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.
- Background: PubMed 28703220Minisola 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.
- Background: PubMed 18365315Bastepe 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.
- Background: PubMed 21538511Carpenter 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.
- Background: PubMed 12419819Saito 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.
- Background: PubMed 16358214Bergwitz 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.
- Background: PubMed 25123121Nielsen 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.
- Background: PubMed 19837909Peacock 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.
- Background: PubMed 17401693Karp 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.
- Individual participant dataSharing planned: Yes. Publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels Birkebæk., MD, PhD principal investigator
Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Phosphate tablets., High cheese intake. and High milk intake. in people with Hypophosphatemic Rickets, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum phosphate. (time frame: Three days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03348644, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2017.