Characterising Pain, QoL, Body Composition, Arterial Stiffness, Muscles and Bones in Adult Persons With XLH and Healthy Controls

NCT04273490 | Completed

• 1 other identifier: 1107214219
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

Hereditary hypophosphatemia (XLH) is a rare, inherited disease. Loss-of-function mutation in the phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) results in excess fibroblast growth factor 23 (FGF23) production and manifests as rickets in children and osteomalacia in adults. This study aims to characterize and measure pain, quality of life, muscle function, body composition, arterial stiffness, bone mineral density, geometry and microarchitecture in patients with XLH compared to age and gender-matched controls.

Conditions

X-linked Hypophosphatemia; Hereditary Hypophosphatemia

Outcome Measures

Primary Outcomes (29)

• PPT

  Pressure pain threshold assessed by pressure algometry

  Day 2

• Quality of life in patients with bone-specific pain

  Assessed by questionnaire (FACT-BP) on a scale from 0 to 4. Higher scores mean a worse outcome.

  Day 1

• General pain: Brief Pain Inventory

  Assessed by questionnaire (Brief Pain Inventory) on a scale from 0 to 10. 0 meaning no pain, 10 meaning worst pain ever.

  Day 1

• Neuropathic pain: questionnaire (painDETECT)

  Assessed by questionnaire (painDETECT) on a scale from 0 to 10. 0 meaning no pain, 10 meaning worst pain ever.

  Day 1

• Health-related quality of life: SF36v2

  Assessed by questionnaire (SF36v2) on a scale from 1 to 5. Higher scores meaning a worse outcome.

  Day 1

• Systolic and diastolic blood pressure

  24 hour blood pressure of the upper right arm

  24 hours

• Pulse wave velocity

  Assessed by tonometry using SphygmoCor system

  45 minutes

• Arterial stiffness

  Assessed by tonometry using SphygmoCor system

  45 minutes

• Arterial stiffness

  Assessed by tonometry using Arteriograph24

  24 hours

• Maximum strength

  Handgrip strength, elbow and knee flexion and extension assessed by dynamometer chair (Good Strength; Metitur Ltd, Finland).

  Day 2

• Maximal force production

  Handgrip strength, elbow and knee flexion and extension assessed by dynamometer chair (Good Strength; Metitur Ltd, Finland).

  Day 2

• Timed Up and Go

  Measures the time to stand up, walk three metres in a straight line, and immediately return to the chair.

  Day 2

• Repeated chair rising

  Measures the time for ten consecutive chair rises.

  Day 2

• Repeated weight lifting

  Measures the time for ten consecutive weight lifts.

  Day 2

• 6-minutes' walk test

  Measures the distance walked in 6 minutes.

  Day 1

• Body composition

  Assessed by DXA

  Day 2

• Vertebral Fracture Assessment

  Assessed by DXA

  Day 2

• Volumetric bone mineral density

  Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy

  Day 1

• Bone geometry

  Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy

  Day 1

• Bone microarchitecture

  Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy

  Day 1

• Estimated bone strength

  Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy

  Day 1

• Mineralization rate

  Histomorphometry on bone biopsy

  14 days

• Mineralization lag time

  Histomorphometry on bone biopsy

  14 days

• Osteoid volume

  Osteoid volume in trabecular and compact bone assessed by histomorphometry on bone biopsy

  14 days

• Osteoid thickness

  Osteoid thickness in trabecular and compact bone assessed by histomorphometry on bone biopsy

  14 days

• Osteoid surface covering

  Osteoid surface covering in trabecular and compact bone assessed by histomorphometry on bone biopsy

  14 days

• Percentage of surface covered by osteoblasts

  Assessed by histomorphometry on bone biopsy

  14 days

• Percentage of surface covered by osteoclasts

  Assessed by histomorphometry on bone biopsy

  14 days

• Lacunar concentration of mineralization inhibitors

  Assessed by nano-scale on bone biopsy

  14 days

Secondary Outcomes (3)

• Catastrophic thinking

  Day 1

• Depression

  Day 1

• Anxiety

  Day 1

Other Outcomes (22)

• Smallest distance between knees.

  Day 1

• Smallest distance between ankles.

  Day 1

• Joint mobility

  Day 1

Study Arms (2)

Hereditary hypophosphatemia

Adult persons with genetically or biochemically verified hereditary hypophosphatemia.

Control

Adult control persons without disturbances in calcium, vitamin D or phosphate homeostasis matched on age, gender and menopausal status.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

50 persons with hereditary hypophosphatemia and 50 control persons without disturbances in the calcium, vitamin D or phosphate homeostasis, matched by age (+/- 2 years) and gender. For women, matching will also be performed on menopausal status (pre-, peri-, and postmenopausal\*). \*Pre-menopausal = regular periods Peri-menopausal = irregular periods +/- hot flashes Post-menopausal = last period ≥1 year ago

You may qualify if:

• Understand oral and written Danish
• Able to consent
• For XLH only:
• genetically verified XLH by detection of a disease-causing mutation in PHEX or a positive family history of X-linked hypophosphatemia.
• biochemically verified hereditary hypophosphatemia: serum PO4 below normal range and low TmPO4/GFR, and/or elevated serum FGF23 and a history of childhood rickets or spontaneous endodontic abscesses to exclude acquired hypophosphatemia, e.g., tumor-induced osteomalacia.

You may not qualify if:

• P-25OHD \< 25 mmol/L\*
• Severe co-morbidities, which in the opinion of the investigator may have major impact on study outcomes. This may include, but is not limited to o poorly controlled hyperthyroidism o Paget disease
• o type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus
• o severe and chronic cardiac, liver, or renal disease
• o Cushing syndrome
• o Rheumatoid arthritis
• o Active pancreatitis
• o Malnutrition
• o Recent prolonged immobility\*
• o Active malignancy (including myeloma)
• Treatment with
• o Burosumab
• Beta-blockers
• Oral steroids
• For controls only:

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Dept. of Endocrinology and Internal Medicine, The Osteoporosis Clinic

Aarhus N, 8200, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, white cells, urine, and bone tissue.

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets

Condition Hierarchy (Ancestors)

Rickets, Hypophosphatemic; Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Hypophosphatemia; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Study Officials

• Lars Rejnmark

  Dept. of Endocrinology and Internal Medicine, The Osteoporosis Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2019
• First Posted: February 18, 2020
• Study Start: February 18, 2020
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: November 29, 2023

Record last verified: 2023-05

Locations

DK (1)