Effects of Serotonin Excess on Bone in Carcinoid Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Carcinoid Syndrome

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• United Kingdom
  • South Yorks
    • Sheffield, South Yorks, United Kingdom, S5 7AU
      • Academic Unit of Bone Metabolism (Sheffield)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Men and women age 18 years or older with carcinoid syndrome attending the Sheffield neuro-endocrine tumour clinic Healthy men and women individually matched to the patients by gender, age, height and BMI

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Carcinoid syndrome; Patients: Men and women age 18 years or older with carcinoid syndrome attending the Sheffield neuro-endocrine tumour clinic
Healthy Volunteers; Control group: Healthy men and women individually matched to the patients by gender, age, height and BMI

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Collaborators: University of Sheffield
• Investigators: Principal Investigator: Jennifer S Walsh, PhD, Sheffield Teaching Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: August 26, 2011
• First Submitted That Met QC Criteria: September 7, 2011
• First Posted (Estimate): September 8, 2011

Study Record Updates

• Last Update Posted (Estimate): June 15, 2012
• Last Update Submitted That Met QC Criteria: June 14, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Drug-Related Side Effects and Adverse Reactions; Syndrome; Carcinoid Tumor; Malignant Carcinoid Syndrome; Serotonin Syndrome
• Other Study ID Numbers: STH15805

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No