Text Size

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
History of Changes
  Purpose

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

Condition Intervention
Obesity
 Other: Study visit procedures

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Relationships Between GLP-2 and Markers of Bone Turnover Following Feeding: the Influence of Obesity and Cellular Mechanisms of Action

Resource links provided by NLM:

MedlinePlus related topics: Obesity
U.S. FDA Resources

Further study details as provided by Sheffield Teaching Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • GLP-2 levels [ Time Frame: Change at 20, 60 and 120 minutes ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples Without DNA

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.


Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Obese
Premenopausal women, 25 - 40 years with BMI of ≥30kg/m2
 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.
Lean
Premenopausal women, 25 - 40 years with BMI of 18.5-24.9 kg/m2
 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.

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   25 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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.

Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01531907

Locations
United Kingdom
Academic Unit of Bone Metabolism
Sheffield, South Yorkshire, United Kingdom, S5 7AU
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Academic Unit of Bone Metabolism
Investigators
Principal Investigator: Paul Dimitri, Dr Sheffield Childrens Hospital
  More Information

No publications provided

Responsible Party: Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01531907     History of Changes
Other Study ID Numbers: STH16160
Study First Received: February 3, 2012
Last Updated: December 14, 2012
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
GLP2
Obesity
Premenopausal
 Bone
Formation
Resorption

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
 Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on May 23, 2013