ClinicalTrials.gg
CompletedNCT03748966Updated May 7, 2026Results posted

Calcitriol Monotherapy for X-Linked Hypophosphatemia

An Early Phase 1 interventional study of Calcitriol in X-linked Hypophosphatemia, Hypophosphatemic Rickets and Hypophosphatemic Rickets, X-Linked Dominant, sponsored by Massachusetts General Hospital. Completed at 1 site in United States. Open to participants aged 3 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-05-07.

Sponsored by Massachusetts General Hospital · Early Phase 1, Interventional, and Treatment

Phase
Early Phase 1
Study type
Interventional
Enrollment
16
Allocation
Non-randomized
Ages
3 Years to 70 Years
Sex
All
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Study summary

Children and adults with XLH recruited will be treated with calcitriol alone (without phosphate supplementation) for one year, during which the calcitriol dose will be escalated during the first 3 months of therapy. The investigators hypothesize that treatment of adults and children with XLH alone will improve serum phosphate levels and skeletal mineralization without causing an increase in kidney calcifications. The study will also examine if calcitriol therapy will improve growth in children.

02

Conditions studied

  • X-linked Hypophosphatemia
  • Hypophosphatemic Rickets
  • Hypophosphatemic Rickets, X-Linked Dominant

Keywords

  • XLH
  • calcitriol
  • x-linked hypophosphatemia
  • rickets
  • 1,25 dihydroxyvitamin D
  • bone disorder
  • rare bone disease
  • vitamin D
  • hypophosphatemic rickets
03

In context

Familial Hypophosphatemic Rickets

49 studies on the registry are indexed under Familial Hypophosphatemic Rickets; 8 are open to participants now.

This study's enrollment of 16 is below the median of 28 across 29 interventional studies indexed under Familial Hypophosphatemic Rickets.

Browse Familial Hypophosphatemic Rickets studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,586 studies on the registry; 447 are open to participants now.

Of its 222 completed or terminated interventional studies of FDA-regulated products, 168 (76%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
3 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Clinical diagnosis of XLH with family history excluding male-to-male transmission, or positive genotype for PHEX mutation
  • Serum PTH levels less than 1.5x the
  • Serum calcium levels less than 10.0 mg/dl
  • >= 60 mL/min/1.73m2
  • 25(OH) vitamin D level >= 20 ng/dL

Exclusion criteria

Exclusion Criteria:

  • Known allergy to calcitriol
  • Pregnancy or breast feeding
  • Use of skeletally active agents such as bisphosphonates, teriparatide, SERMS, hormone replacement therapy and progesterone-only agents (combination oral contraceptive use in premenopausal women is not an exclusion criterion).
  • Unwilling or unable to stop therapy with calcitriol and phosphate therapy for two weeks prior to study
  • Therapy with cinacalcet within the past two weeks
  • Current use of growth hormone therapy
  • Use of diuretics or medications that alter renal handling of mineral ions.
  • Use of for more than 14 days in the past 12 months with the exception of inhaled agents.
  • History of except basal and squamous cell carcinoma of the skin.
  • Significant history of psychiatric disease per .
  • Substance use disorder per DSM-5.
  • Significant cardiopulmonary disease (unstable CAD or stage D ACC/AHA heart failure).
  • Absence of laboratory values for serum calcium, phosphate and creatinine in the 24 months prior to enrollment.
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

DSM diagnostic criteria

The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.

05

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • Experimental
    Adults with XLH

    Adults with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year

    Drug: Calcitriol

  • Experimental
    Children with XLH

    Children (age 3-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year

    Drug: Calcitriol

Interventions

  • Adults and children (age 3-17) with X-linked hypophosphatemia will be treated with calcitriol therapy without phosphate supplementation. Doses of calcitriol will be escalated and optimized in the first three months of the study. Calcitriol is an oral medication taken once a day.

    Also known as: 1,25 dihydroxyvitamin D

06

What researchers measure

Primary outcomes

  1. Change in Serum Phosphate in Adults and Children With XLH Between Baseline and 12 Months

    serum phosphate

    Time frame: baseline and 12 months

  2. Change From Baseline in TmP/GFR in Adults and Children With XLH

    a measure of kidney resorption of phosphate

    Time frame: baseline and 12 months

  3. Rickets Score for Children With XLH

    a score of rickets severity determined by reading x-rays of wrists and knees (10 point Thacher score with 0 being normal and 10 being severe)

    Time frame: baseline and 12 months

  4. Change From Baseline in Nephrocalcinosis Grade

    determine if there is change in amount of calcifications in the kidneys: graded from grade 0 (normal) to grade IV (stone formation, solitary focus of echos at the tip of the renal pyramid)

    Time frame: baseline and 12 months

Secondary outcomes

  1. Growth in Children With XLH

    Z-score of growth (this is full name of variable)- number represents standard deviation above or below the known mean of the general population at the corresponding age. Z score that is positive is above the mean, negative is below the mean.

    Time frame: baseline and 12 months

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Results

Posted May 7, 2026

Participant flow

6 children with XLH were enrolled - Due to COVID and approval of burosumab, difficult to recruit children with XLH into trial 10 adults with XLH were enrolled

Participant flow — Overall Study
MilestoneAdults With XLHChildren With XLH
Started106
Completed86
Not completed20
Withdrew: Lost to follow-up10
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryChange in Serum Phosphate in Adults and Children With XLH Between Baseline and 12 Months

serum phosphate

Time frame:
baseline and 12 months
Reported as:
Mean · mg/dl
Change in Serum Phosphate in Adults and Children With XLH Between Baseline and 12 Months
mg/dlAdults With XLHChildren With XLH
Change in Serum Phosphate in Adults and Children With XLH Between Baseline and 12 Months2.6 ± 0.52.1 ± 0.3
Statistical analysis
  • Adults With XLH · t-test, 2 sided · p = 0.318 (compare baseline with 12 month data)
  • Children With XLH · t-test, 2 sided · p = 0.497 (compare baseline with 12 month data)
PrimaryChange From Baseline in TmP/GFR in Adults and Children With XLH

a measure of kidney resorption of phosphate

Time frame:
baseline and 12 months
Reported as:
Mean · percent
Change From Baseline in TmP/GFR in Adults and Children With XLH
percentAdults With XLHChildren With XLH
Change From Baseline in TmP/GFR in Adults and Children With XLH88.49 ± 3.689.08 ± 5.9
Statistical analysis
  • Adults With XLH · t-test, 2 sided · p = 0.114
  • Children With XLH · t-test, 2 sided · p = 0.391
PrimaryRickets Score for Children With XLH

a score of rickets severity determined by reading x-rays of wrists and knees (10 point Thacher score with 0 being normal and 10 being severe)

Time frame:
baseline and 12 months
Reported as:
Mean · rickets score
Rickets Score for Children With XLH
rickets scoreChildren With XLH
Rickets Score for Children With XLH1.6 ± 0.5
Statistical analysis
  • Children With XLH · t-test, 2 sided · p = 0.215
PrimaryChange From Baseline in Nephrocalcinosis Grade

determine if there is change in amount of calcifications in the kidneys: graded from grade 0 (normal) to grade IV (stone formation, solitary focus of echos at the tip of the renal pyramid)

Time frame:
baseline and 12 months
Reported as:
Mean · nephrocalcinosis score
Change From Baseline in Nephrocalcinosis Grade
nephrocalcinosis scoreAdults With XLHChildren With XLH
Change From Baseline in Nephrocalcinosis Grade1.15 ± 0.821.11 ± 0.97
Statistical analysis
  • Adults With XLH · t-test, 2 sided · p = 0.186
  • Children With XLH · t-test, 2 sided · p = 0.274
SecondaryGrowth in Children With XLH

Z-score of growth (this is full name of variable)- number represents standard deviation above or below the known mean of the general population at the corresponding age. Z score that is positive is above the mean, negative is below the mean.

Time frame:
baseline and 12 months
Reported as:
Mean · z score
Growth in Children With XLH
z scoreChildren With XLH
Growth in Children With XLH-1.5 ± 1.1
Statistical analysis
  • Children With XLH · t-test, 2 sided · p = 0.615

Adverse events

Collected over from enrollment visit through 12 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Adults With XLH0/10 (0%)0/10 (0%)2/10 (20%)
Children With XLH0/6 (0%)1/6 (16.7%)5/6 (83.3%)
Most frequent serious events
Most frequent serious events
EventAdults With XLHChildren With XLH
Tooth abscessMusculoskeletal and connective tissue disorders0/101/6
Most frequent other events
Most frequent other events
EventAdults With XLHChildren With XLH
HypercalciuriaRenal and urinary disorders0/102/6
bubble in gums that looks like tooth abscess but did not require treatmentMusculoskeletal and connective tissue disorders1/101/6
gingival inflammationMusculoskeletal and connective tissue disorders0/101/6
ConstipationGastrointestinal disorders0/101/6
strep pharyngitisInfections and infestations0/101/6
fatigueGeneral disorders0/101/6
stable fibrous cortical defect in right femurMusculoskeletal and connective tissue disorders0/101/6
elevated LFTsMusculoskeletal and connective tissue disorders1/100/6

Baseline characteristics

Age, Continuous
Age, Continuous(years)Adults With XLHChildren With XLHTotal
Mean29.2 ± 11.611.1 ± 3.622.44 ± 12.31
Sex: Female, Male
Sex: Female, Male(Participants)Adults With XLHChildren With XLHTotal
Female9413
Male123
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Adults With XLHChildren With XLHTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American101
White9615
More than one race000
Unknown or Not Reported000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Adults With XLHChildren With XLHTotal
Hispanic or Latino000
Not Hispanic or Latino10616
Unknown or Not Reported000
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Study locations

1 site
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
09

References and documents

Publications

  • Liu ES, Martins JS, Raimann A, Chae BT, Brooks DJ, Jorgetti V, Bouxsein ML, Demay MB. 1,25-Dihydroxyvitamin D Alone Improves Skeletal Growth, Microarchitecture, and Strength in a Murine Model of XLH, Despite Enhanced FGF23 Expression. J Bone Miner Res. 2016 May;31(5):929-39. doi: 10.1002/jbmr.2783. Epub 2016 Feb 2. PubMed 26751835 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 7, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03748966
Responsible party
Eva Liu (Assistant Professor of Medicine, Massachusetts General Hospital) — Principal investigator
First posted
Nov 21, 2018
Start date
Mar 28, 2019
Primary completion
Mar 1, 2025
Completion
Feb 26, 2026
Results posted
May 7, 2026
Last update
May 7, 2026

Study contacts

Eva Liu, MD
principal investigator · Massachusetts General Hospital and Brigham and Women's Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Calcitriol

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