Effects of Serotonin Excess on Bone in Carcinoid Syndrome

Completed

• Conditions: Carcinoid Syndrome

• Registration Number: NCT01430871
• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Brief Summary

Serotonin has recently been identified as a major regulator of bone formation. Gut-derived serotonin inhibits bone formation, and early animal studies have shown that inhibition of gut-derived serotonin has anabolic effects on bone in ovariectomised rodents. This pathway has potential to be developed as a new anabolic treatment for osteoporosis in humans.

Carcinoid neuro-endocrine tumours produce very high levels of serotonin, and so it might be expected that patients with carcinoid disease would have reduced bone formation, low bone mass and fractures. However, this has not been apparent in clinical practice. There may be a discrepancy between rodent models and human disease. This study aims to identify whether patients with carcinoid disease have reduced bone mass, reduced bone formation or high fracture rates. The investigators will conduct a cross-sectional observational case-control study of patients with carcinoid disease in the Sheffield neuro-endocrine tumour clinic and gender-, age- and body mass index (BMI)-matched controls.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-08-26
• Study First Submitted QC: 2011-09-07
• Study First Posted: 2011-09-08
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Status Verified: 2012-06
• Last Update Submitted: 2012-06-14
• Last Update Posted: 2012-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• Willing to participate
• Able to give informed consent
• Patient with carcinoid syndrome-active disease (untreated or receiving medical treatment)
• or
• Healthy volunteer who adequately matches a patient with carcinoid syndrome gender, age (±5 years), height (±5cm) and BMI(±3 kg/m2)

Exclusion Criteria

• Curative surgery for carcinoid disease

• Body weight over 159 kg (weight limit for DXA measurement of BMD)

• Previous orthopaedic surgery or fractures which preclude imaging at all sites

• History of any long term immobilization (duration greater than three months)

• Fracture less than one year prior to recruitment

• Current pregnancy or trying to conceive

• Delivery of last child less than one year prior to recruitment

• Breast feeding less than one year prior to recruitment

• History of, or current conditions known to affect bone metabolism

  • Diagnosed skeletal disease or inflammatory arthritis
  • Chronic renal disease
  • Malabsorption syndromes
  • Other diagnosed endocrine disorders
  • Hypocalcemia or hypercalcemia
  • Diagnosed restrictive eating disorder
  • Diabetes mellitus

• Conditions or surgery which prevent the acquisition or analysis of DXA, VFA or HR-pQCT

• Use of medications or treatment known to affect bone metabolism

• Alcohol intake greater than 21 units per week

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Lumbar spine and total hip Bone Mineral Density BMD) measured by Dual-emission X-ray absorptiometry (DXA)

Secondary Outcome Measures

Name	Time	Method
Self-reported fracture history
Serum osteocalcin
Radius and tibia geometry and microarchitecture by HR-pQCT
Serum type 1 procollagen (N-terminal)(PINP)
Carboxy-terminal collagen crosslinks (CTX)
Vertebral fracture assessment
Blood serotonin and 5HIAA
24h urine 5HIAA	24 hours
Bone Alkaline Phosphatase (BAP)

Trial Locations

Locations (1)

Academic Unit of Bone Metabolism (Sheffield); 🇬🇧 Sheffield, South Yorks, United Kingdom