Brain-gut Interaction in Irradiated Patients With Acromegaly

NCT02005978 | Unknown

• 1 other identifier: ACRO-INC-TME
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Acromegaly is caused by increased production of growth hormone (GH) from a usually benign pituitary tumor. The disease causes a number of complications including disturbances in glucose metabolism and about 25% of the patients develop diabetes. Most patients are cured upon surgery alone, but many require additional medical treatment, and in rare cases radiotherapy. A disadvantage of radiotherapy is a risk of radiation damage to nearby areas such as the hypothalamus. The true extent of irradiation induced hypothalamic dysfunction, however, remains uncertain. Data have shown significant improvement and often normalization of glucose metabolism upon surgical cure from acromegaly, whereas data suggest that such improvement is less likely in patients receiving additional radiotherapy. The hypothalamus is part of the so-called 'gut-brain axis', where gastrointestinal hormones through interaction with the hypothalamus plays a significant role in the regulation of appetite and glucose metabolism. Incretins are the most prominent gastrointestinal hormones involved, with the incretin-effect referring to food-induced insulin secretion, which in healthy subjects is responsible for up to 70% of the insulin response after oral glucose intake. The investigators hypothesize that radiation conditional influence of the hypothalamus may compromise the gut-brain activity and thereby affect the incretin-effect and gastrointestinal-mediated glucose disposal (GIGD; i.e. sum of all gastrointestinal-derived factors that contribute to glucose metabolism) in patients with acromegaly. The aim of the study is to investigate the long term effect of surgery with or without additional fractionated radiation therapy on glucose metabolism as assessed by incretin-effect and GIGD in acromegaly, in order to identify possible associations with treatment modality. The study population include 24 acromegalic patients who have previously received (N=12) or did not receive (N=12) pituitary irradiation as part of their treatment, and 12 matched healthy controls.

Conditions

Acromegaly

Outcome Measures

Primary Outcomes (1)

• Measure the incretin effect during glucose tolerance tests in acromegaly

  Extended oral glucose tolerance test (OGTT), followed by isoglycaemic intravenous glucose infusion (IGII) with concurrent measurement of plasma-glucose, -insulin, -C-peptide, -glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) at fixed time-points.

  one year

Study Arms (3)

Acromegaly1

Acromegalic patients treated with radiation therapy

Healthy controls

Health controls matched for age, gender and BMI to the patients

Acromegaly 2

Acromegalic patients treated with pituitary surgery

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with acromegaly treated with radiation therapy or surgery

You may qualify if:

• Age ≥ 18 years
• Diagnosis of acromegaly, and treated at the department of Endocrinology, Copenhagen University Hospital, Rigshospitalet, Denmark (tertiary referral hospital)

You may not qualify if:

• Diabetes mellitus
• Pregnancy or breastfeeding
• Treatment with medications potentially influencing glucose metabolism, including thiazides and steroids (replacement therapy with hydrocortisone not included but matched for).
• Chronic or earlier events of acute pancreatitis
• Inflammatory bowel disease (Mb. Crohn/ulcerous colitis)
• Bowel resection or larger gastrointestinal surgical interventions
• Blood percent \< 6.5 mmol/L

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• University of Copenhagen: collaborator

Study Sites (1)

National University Hospital, Department of Medical Endocrinology

Copenhagen, DK-2100, Denmark

Location

Related Publications (1)

• Jorgensen NT, Erichsen TM, Jorgensen MB, Idorn T, Feldt-Rasmussen B, Holst JJ, Feldt-Rasmussen U, Klose M. Glucose metabolism, gut-brain hormones, and acromegaly treatment: an explorative single centre descriptive analysis. Pituitary. 2023 Feb;26(1):152-163. doi: 10.1007/s11102-022-01297-x. Epub 2023 Jan 6.

  PMID: 36609655 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples

MeSH Terms

Conditions

Acromegaly

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Ulla Feldt-Rasmussen, Professor

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, chief physician

Study Record Dates

• First Submitted: November 18, 2013
• First Posted: December 9, 2013
• Study Start: April 1, 2013
• Primary Completion: July 1, 2017
• Study Completion: December 1, 2017
• Last Updated: September 20, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)