Clinical trial NCT02518737: Examination of the Postprandial Bone Remodeling in Persons With Reduced GIP-Receptor Activity
Official title: Examination of the Postprandial Bone Remodeling in Persons With Reduced Activity of the Receptor for the Enteric Hormone Glucose-dependent Insulinotropic Polypeptide
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bone Remodeling
Keywords: Glucose-dependent Insulinotropic Polypeptide
Receptor Deficiency
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Glostrup University Hospital, Copenhagen
name: The Novo Nordisk Foundation Center for Basic Metabolic Research
First posted: 2015-08-10
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The groups will be recruited from the Helbred2006 cohort, Glostrup Hospital, Denmark.

Brief summary: The bone tissue of the human adult body is in a constant process of break-down (resorption) and rebuilding (formation), a process called bone remodeling. The extent to which bone remodeling happens varies during the day, especially a decrease in the bone resorption is observed after eating.

The overall purpose of this study is to examine the possible role of the hormone Glucose-dependent Insulinotropic Polypeptide (GIP) in Bone Remodeling. GIP is released from cells in the gut after eating, and previous studies have shown an effect of GIP on bone tissue. In addition, it has been observed that the risk of bone fracture is 60% higher in women with a mutation in the GIP receptor, when compared to women with a normal functioning GIP receptor.

In the present study humans with a mutation in their GIP receptor is compared to humans with a normal functioning GIP receptor. The study population will be examined during a meal stimulation test, where blood will be sampled regularly. The blood samples will be examined for markers of bone resorption among other markers of bone remodeling, GIP and other gut hormones.

The hypothesis for the present study is that GIP secreted after meal ingestion inhibits bone resorption. Thus it is expected that the decrease in resorption is less pronounced in the humans carrying the GIP-receptor mutation, compared to humans with a normal functioning GIP receptor.


Eligibility criteria: Inclusion Criteria:

* Verified mutation (Glu354Gln) of the GIP-receptor

Exclusion Criteria:

* Type 2 diabetes
* Pregnancy
* Previous long-lasting treatment with steroids
* On-going steroid treatment (with the exception of inhalation-steroids)
* Osteoporosis

Primary outcomes:
measure: CTx
timeFrame: 7, 15, 30, 45, 60, 90, 120, 150, 180, 240 minutes after intake of the meal test.
Secondary outcomes:
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Biomedical Sciences, University of Copenhagen
Study officials:
affiliation: University of Copenhagen
name: Bolette Hartmann, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C. Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone. 2002 Jul;31(1):57-61. doi: 10.1016/s8756-3282(02)00791-3.
citation: Nielsen HK, Brixen K, Kassem M, Christensen SE, Mosekilde L. Diurnal rhythm in serum osteocalcin: relation with sleep, growth hormone, and PTH(1-84). Calcif Tissue Int. 1991 Dec;49(6):373-7. doi: 10.1007/BF02555845.
citation: Nissen A, Christensen M, Knop FK, Vilsboll T, Holst JJ, Hartmann B. Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans. J Clin Endocrinol Metab. 2014 Nov;99(11):E2325-9. doi: 10.1210/jc.2014-2547. Epub 2014 Aug 21.
citation: Torekov SS, Harslof T, Rejnmark L, Eiken P, Jensen JB, Herman AP, Hansen T, Pedersen O, Holst JJ, Langdahl BL. A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk. J Clin Endocrinol Metab. 2014 Apr;99(4):E729-33. doi: 10.1210/jc.2013-3766. Epub 2014 Jan 21.