Clinical trial NCT01430871: Effects of Serotonin Excess on Bone in Carcinoid Syndrome
Official title: Effects of Serotonin Excess on Bone in Carcinoid Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Carcinoid Syndrome
Lead sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Sheffield
First posted: 2011-09-08
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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.


Eligibility criteria: 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

Primary outcomes:
measure: Lumbar spine and total hip Bone Mineral Density BMD) measured by Dual-emission X-ray absorptiometry (DXA)
Secondary outcomes:
measure: Self-reported fracture history
measure: Vertebral fracture assessment
measure: Radius and tibia geometry and microarchitecture by HR-pQCT
measure: Serum osteocalcin
measure: Blood serotonin and 5HIAA
measure: 24h urine 5HIAA
timeFrame: 24 hours
measure: Serum type 1 procollagen (N-terminal)(PINP)
measure: Bone Alkaline Phosphatase (BAP)
measure: Carboxy-terminal collagen crosslinks (CTX)
Other outcomes:
Locations:
city: Sheffield
country: United Kingdom
facility: Academic Unit of Bone Metabolism (Sheffield)
state: South Yorks
Study officials:
affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
name: Jennifer S Walsh, PhD
role: PRINCIPAL_INVESTIGATOR
References: