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Brain-gut Interaction in Irradiated Patients With Acromegaly

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ClinicalTrials.gov Identifier: NCT02005978
Recruitment Status : Unknown
Verified September 2016 by Ulla Feldt-Rasmussen, Rigshospitalet, Denmark.
Recruitment status was:  Active, not recruiting
First Posted : December 9, 2013
Last Update Posted : September 20, 2016
Sponsor:
Collaborator:
University of Copenhagen
Information provided by (Responsible Party):
Ulla Feldt-Rasmussen, Rigshospitalet, Denmark

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.


Condition or disease
Acromegaly

Detailed Description:

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.

Design: observational case-control study Participants: 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.

Investigation: 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.


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Study Type : Observational
Estimated Enrollment : 36 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Incretin Effect and Gastrointestinally Mediated Glucose Disposal in Cranially Irradiated Patients With Acromegaly
Study Start Date : April 2013
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


Group/Cohort
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



Primary Outcome Measures :
  1. Measure the incretin effect during glucose tolerance tests in acromegaly [ Time Frame: one year ]
    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.


Biospecimen Retention:   Samples Without DNA
Blood samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with acromegaly treated with radiation therapy or surgery
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02005978


Locations
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Denmark
National University Hospital, Department of Medical Endocrinology
Copenhagen, Denmark, DK-2100
Sponsors and Collaborators
Rigshospitalet, Denmark
University of Copenhagen
Investigators
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Principal Investigator: Ulla Feldt-Rasmussen, Professor Rigshospitalet, Denmark

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Responsible Party: Ulla Feldt-Rasmussen, Professor, chief physician, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02005978     History of Changes
Other Study ID Numbers: ACRO-INC-TME
First Posted: December 9, 2013    Key Record Dates
Last Update Posted: September 20, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases