Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Academic Unit of Bone Metabolism
Information provided by (Responsible Party):
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01531907
First received: February 3, 2012
Last updated: December 14, 2012
Last verified: December 2012

February 3, 2012
December 14, 2012
September 2011
September 2013   (final data collection date for primary outcome measure)
GLP-2 levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]
GLP-2 levels [ Time Frame: Up to 120 minutes ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01531907 on ClinicalTrials.gov Archive Site
  • Osteocalcin levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]
  • β Carboxy-terminal collagen crosslinks (β CTx)levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]
  • Procollagen 1 N-terminal propeptide (P1NP) levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]
  • High-resolution peripheral quantitative computed tomography (HRpQCT) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
  • Dual-emission X-ray absorptiometry (DXA) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
  • Osteocalcin levels [ Time Frame: Up to 120 minutes ] [ Designated as safety issue: No ]
  • β Carboxy-terminal collagen crosslinks (β CTx)levels [ Time Frame: Up to 120 minutes ] [ Designated as safety issue: No ]
  • Procollagen 1 N-terminal propeptide (P1NP) levels [ Time Frame: Up to 120 minutes ] [ Designated as safety issue: No ]
  • High-resolution peripheral quantitative computed tomography (HRpQCT) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
  • Dual-emission X-ray absorptiometry (DXA) [ Time Frame: At baseline ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding
Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding: the Influence of Obesity and Cellular Mechanisms of Action

This study has been designed to study differences bone turnover in relation to glucagon-like peptide-2 (GLP-2) following feeding in lean and obese premenopausal women. Given the preliminary evidence that GLP-2 may act directly on osteoclasts, the investigators plan to determine whether GLP2 receptors are expressed in osteoclasts and the effect of GLP-2 on bone resorption.

Hypotheses:

  1. Acute responses of GLP-2 and bone resorption markers following feeding are affected by body fat mass.
  2. Serum levels of GLP-2 are lower in obese pre-menopausal women and are associated with a reduction in trabecular and/or cortical bone mass
  3. GLP-2 has direct actions on osteoclast resorption via a functional receptor

Study objectives:

  1. To determine if differences in baseline serum levels of GLP-2 are related to differences in bone microarchitecture, structure and strength at the distal tibia and distal radius between obese and lean premenopausal females.
  2. To determine whether obesity in premenopausal females influences levels of circulating GLP-2 following a standardised glucose meal with a resultant change in markers of bone formation and resorption
  3. To test whether GLP-2 directly affects osteoclast function via an identifiable receptor
Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

On completion of the study, serum and plasma aliquots will be moved to the Human Tissue Authority (HTA) licensed biorepository housed in the Centre for Biomedical Research.

Non-Probability Sample

The investigators will recruit healthy pre-menopausal, Caucasian female participants 25-40 years and divide them into two groups, obese and lean according to their Body Mass Index. Participants will be identified and approached from a study group of obese and lean participants previously recruited for the 'The Effects of Obesity on Bone Structure and Strength - Fat and Bone Study (FAB)' study (REC ref 10/H1308/61) conducted at the Academic Unit of Bone Metabolism (AUBM) in Sheffield. Participants from this study have been selected as some of the scan and neuromuscular function data generated from this study will be reused as explained below. Body Mass Index ≥30 kg/m2 will be used to define obesity with BMI for lean participants defined as 18.5-24.9 kg/m2. Thirty participants will be recruited, 15 obese and 15 lean. Participants will be matched for age, and where possible height.

Obesity
Other: Study visit procedures

Anthropometric measurements to include:

  • Weight, height, and BMI.
  • Waist and hip circumference
  • Triceps skinfold thickness
  • Measurement of supine abdominal thickness A baseline blood sample (15ml)is taken before receiving a standard polycal drink (75g glucose load) Three further blood samples (15 ml) will be taken, at the time points 20, 60 and 120 minutes after glucose loading. In 10 subjects (5 lean and 5 obese) we will take an additional blood sample (up to 50 ml) at baseline into heparin to grow osteoclasts in culture. Visit duration - approximately 3-4 hours.
  • Obese
    Premenopausal women, 25 - 40 years with BMI of ≥30kg/m2
    Intervention: Other: Study visit procedures
  • Lean
    Premenopausal women, 25 - 40 years with BMI of 18.5-24.9 kg/m2
    Intervention: Other: Study visit procedures
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Enrolling by invitation
30
September 2014
September 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age 25-40
  • Caucasian
  • Premenopausal
  • Able and willing to consent
  • BMI either 18.5-24.9 kg/m2 or ≥30 kg/m2
  • Completion 'The Effects of Obesity on Bone Structure and Strength' study REC ref 10/H1308/61
  • Consented to be approached for future research studies

Exclusion Criteria:

  • Fracture less than twelve months prior to recruitment
  • History of any long term immobilization (duration greater than three months)
  • Current pregnancy or trying to conceive Pregnancy or breast feeding less than one year prior to recruitment
  • Diabetes mellitus
  • History of or current conditions known to affect bone metabolism, which may include:

    • Diagnosed skeletal disease or osteoarthritis
    • Chronic renal disease
    • Acute or chronic hepatic disease
    • Hyperparathyroidism or Hyperthyroidism
    • Malabsorption syndromes
    • Diagnosed endocrine disorders
    • Diagnosed diabetes mellitus
    • Clinically significant hypocalcemia or hypercalcemia
    • Diagnosed restrictive eating disorder
  • Current or clinically significant previous use of medications or treatment known to affect bone metabolism, for example:

    • Depot medroxyprogesterone or the combined oral contraceptive pill
    • Glucocorticoid therapy
    • Anti-convulsant therapy
    • Bone treatments (e.g. Bisphosphonates)
  • Alcohol intake of greater than 21 units per week
  • Athlete, defined as an individual participating in competitive sport at amateur or professional level
  • Monogenic and obesity syndromes
  • History of cancer within the past 5 years excluding skin cancer non melanomas
Female
25 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01531907
STH16160
No
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
Academic Unit of Bone Metabolism
Principal Investigator: Paul Dimitri, Dr Sheffield Childrens Hospital
Sheffield Teaching Hospitals NHS Foundation Trust
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP