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Calcitriol Monotherapy for X-Linked Hypophosphatemia

Primary Purpose

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

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Calcitriol

About this trial

This is an interventional treatment trial for X-linked Hypophosphatemia focused on measuring XLH, calcitriol, x-linked hypophosphatemia, rickets, 1,25 dihydroxyvitamin D, bone disorder, rare bone disease, vitamin D, hypophosphatemic rickets

Eligibility Criteria

3 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 upper limit of normal
Serum calcium levels less than 10.0 mg/dl
eGFR >= 60 mL/min/1.73m2
25(OH) vitamin D level >= 20 ng/dL

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 contraceptive 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 glucocorticoids for more than 14 days in the past 12 months with the exception of inhaled agents.
History of malignancy except basal and squamous cell carcinoma of the skin.
Significant history of psychiatric disease per DSM-5.
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.

Sites / Locations

Massachusetts General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Adults with XLH

Children with XLH

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change from baseline in serum phosphate in adults and children with XLH

Change from baseline in TmP/GFR in adults and children with XLH

a measure of kidney resorption of phosphate

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)

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)

Secondary Outcome Measures

Growth in children with XLH

Z-score of growth

Full Information

NCT ID

NCT03748966

First Posted

November 19, 2018

Last Updated

March 16, 2022

Sponsor

Massachusetts General Hospital

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

1. Study Identification

Unique Protocol Identification Number

NCT03748966

Brief Title

Calcitriol Monotherapy for X-Linked Hypophosphatemia

Official Title

Calcitriol Monotherapy for X-Linked Hypophosphatemia: Effects on Mineral Ions, Growth and Skeletal Parameters

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 28, 2019 (Actual)

Primary Completion Date

March 2023 (Anticipated)

Study Completion Date

March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

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

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Model Description

Adults or children (age 3-17) with X-linked hypophosphatemia (XLH) will be enrolled the study. All research subjects will be treated with optimized doses of calcitriol alone (without phosphate supplementation) for one year.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Adults with XLH

Arm Type

Experimental

Arm Description

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

Arm Title

Children with XLH

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Calcitriol

Other Intervention Name(s)

1,25 dihydroxyvitamin D

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change from baseline in serum phosphate in adults and children with XLH

Time Frame

up to 12 months

Title

Change from baseline in TmP/GFR in adults and children with XLH

Description

a measure of kidney resorption of phosphate

Time Frame

up to 12 months

Title

Rickets score for children with XLH

Description

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

up to 12 months

Title

Change from baseline in nephrocalcinosis grade

Description

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

up to 12 months

Secondary Outcome Measure Information:

Title

Growth in children with XLH

Description

Z-score of growth

Time Frame

up to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 upper limit of normal Serum calcium levels less than 10.0 mg/dl eGFR >= 60 mL/min/1.73m2 25(OH) vitamin D level >= 20 ng/dL 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 contraceptive 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 glucocorticoids for more than 14 days in the past 12 months with the exception of inhaled agents. History of malignancy except basal and squamous cell carcinoma of the skin. Significant history of psychiatric disease per DSM-5. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Eva S Liu, MD

Phone

16175255412

esliu@bwh.harvard.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Marie Demay, MD

Phone

16177263273

demay@helix.mgh.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eva Liu, MD

Organizational Affiliation

Massachusetts General Hospital and Brigham and Women's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Eva Liu, MD

Phone

617-525-5412

esliu@bwh.harvard.edu

First Name & Middle Initial & Last Name & Degree

Marie Demay, MD

Phone

6177263273

demay@helix.mgh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26751835

Citation

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.

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Calcitriol Monotherapy for X-Linked Hypophosphatemia

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