A Prospective Study of Outcome After Therapy for Acromegaly

Active, not recruiting

• Conditions: Acromegaly
• Interventions: Diagnostic Test: Total body magnetic resonance imaging; Procedure: Surgery for acromegaly; Drug: Medications for acromegaly; Procedure: Adipose Tissue Biopsy

• Registration Number: NCT01809808
• Lead Sponsor: Columbia University

Brief Summary

The purpose of this study is to evaluate hormone values and other markers of disease activity in a cohort of patients with acromegaly at the time of diagnosis and then prospectively after surgical or other treatment. This study is designed to determine blood levels of growth hormone and related hormones and cardiovascular risk markers as well as signs and symptoms of the disease at diagnosis and how these parameters change over time after surgical or other therapy. The investigators will also obtain hormonal data in a group of 50 healthy subjects who will each be studied just once with an oral glucose tolerance test (OGTT). These data will provide a comparison group to the acromegaly subjects.

Detailed Description

Surgical removal of the pituitary tumor is the usual first form of treatment offered, but this is curative in only approximately 70% of patients. If not adequately treated, the disease can have significant morbidity largely due to the development of hypertension, diabetes and malignancy as well as possible loss of vision or other neurologic complications of a large pituitary mass. Inadequately treated acromegaly is also associated with a mortality rate 2-3 fold over the general population. All the mechanisms responsible for the increased morbidity and mortality in acromegaly as well as what biochemical criteria should be used during treatment in order to normalize the increased morbidity and mortality are not known. This study aims to follow patients with acromegaly prospectively from active disease through treatment in order to identify these factors.

Study Timeline

• Study Start: 2003-09
• Study First Submitted: 2012-08-08
• Study First Submitted QC: 2013-03-11
• Study First Posted: 2013-03-13
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-25
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Adult males and females.
• Ages 18 and over.
• Presenting to the PI or one of the sub-investigators for evaluation of acromegaly.
• Must have a biochemical diagnosis of acromegaly consisting of an elevated serum insulin-like growth factor 1 (IGF-1) level. Supportive although not required for entry are an elevated growth hormone (GH) level and a failure of GH to suppress normally after oral glucose administration.
• Willingness to participate in this study's procedures.

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Exclusion Criteria

• Subjects who are unwilling to comply with the procedures outlined in the study.
• Subjects who do not have the ability to fully comprehend the nature of the study, to follow instructions, and/or cooperate with study procedures
• Are unwilling to provide informed consent to participate in the study.

Healthy Subjects

Inclusion Criteria:

• Adult males and females.
• Ages 18 and over.
• Responding to ads for participation or by word of mount.
• No medical problems, no medications, stable weight for 3 months prior to study.
• Willingness to participate in this study's procedures.

Exclusion Criteria:

• Subjects who are unwilling to comply with the procedures outlined in the study.
• Subjects who do not have the ability to fully comprehend the nature of the study, to follow instructions, and/or cooperate with study procedures
• Are unwilling to provide informed consent to participate in the study.
• Failure to meet the inclusion criteria.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Acromegaly Subjects	Medications for acromegaly	People who have a biochemical diagnosis of acromegaly, and will or have already undergone surgery for acromegaly and will be taking medications for acromegaly . Subjects will undergo blood sampling, metabolic rate measurement, adipose tissue biopsy and total body magnetic resonance imaging before and over time after either surgery or medical therapy for acromegaly.
Acromegaly Subjects	Adipose Tissue Biopsy	People who have a biochemical diagnosis of acromegaly, and will or have already undergone surgery for acromegaly and will be taking medications for acromegaly . Subjects will undergo blood sampling, metabolic rate measurement, adipose tissue biopsy and total body magnetic resonance imaging before and over time after either surgery or medical therapy for acromegaly.
Healthy Subjects	Total body magnetic resonance imaging	People who are not diagnosed with acromegaly, responding to flyer or by word of mouth for participation, without medical problems, not taking medications, and with a stable weight for 3 months prior to study. Subjects will undergo blood sampling, total body MRI and adipose tissue biopsy once.
Acromegaly Subjects	Total body magnetic resonance imaging	People who have a biochemical diagnosis of acromegaly, and will or have already undergone surgery for acromegaly and will be taking medications for acromegaly . Subjects will undergo blood sampling, metabolic rate measurement, adipose tissue biopsy and total body magnetic resonance imaging before and over time after either surgery or medical therapy for acromegaly.
Healthy Subjects	Adipose Tissue Biopsy	People who are not diagnosed with acromegaly, responding to flyer or by word of mouth for participation, without medical problems, not taking medications, and with a stable weight for 3 months prior to study. Subjects will undergo blood sampling, total body MRI and adipose tissue biopsy once.
Acromegaly Subjects	Surgery for acromegaly	People who have a biochemical diagnosis of acromegaly, and will or have already undergone surgery for acromegaly and will be taking medications for acromegaly . Subjects will undergo blood sampling, metabolic rate measurement, adipose tissue biopsy and total body magnetic resonance imaging before and over time after either surgery or medical therapy for acromegaly.

Primary Outcome Measures

Name	Time	Method
Biochemical activity of Acromegaly	At 5 years after therapy for acromegaly	The study will assess the status of biochemical disease activity of acromegaly before and after treatment for acromegaly. Blood samples are taken for fasting growth hormone and insulin-like growth factor 1 and growth hormone levels 60, 90 and 120 minutes after oral glucose taken at baseline visit, post-operative or after the initiation of medical therapy at month 1 (fasting blood only), month 3 (fasting blood only), month 6, month 12, and annual assessments for at least 5 years.

Secondary Outcome Measures

Name	Time	Method
Visceral Adipose Tissue Mass	Before therapy, 6 months, 1 year and 2 years after the intervention, surgery or medical therapy.	Total Body Magnetic Resonance Imaging
Intra-hepatic Lipid	Before therapy, 6 months, 1 year and 2 years after the intervention, surgery or medical therapy.	Proton magnetic resonance spectroscopy of liver
Resting metabolic rate	Before, 1 year and 2 years after the intervention	Measurement of resting metabolic rate by indirect calorimetry
Plasma Levels of ghrelin	Before, 1 month, 3 months, 6 months, 1 year and 2 years after intervention	Levels of ghrelin in peripheral blood
Plasma Levels of AgRP	Before, 1 month, 3 months, 6 months, 1 year and 2 years after intervention	Levels of AgRP in peripheral blood
Plasma Levels of GLP1	Before, 1 month, 3 months, 6 months, 1 year and 2 years after intervention	Levels of GLP1 in peripheral blood
Serum Levels of insulin	Before, 1 month, 3 months, 6 months, 1 year and 2 years after intervention	Levels of insulin in peripheral blood
Intra-myocellular lipid	Before therapy, 6 months, 1 year and 2 years after the intervention, surgery or medical therapy.	Proton magnetic resonance spectroscopy of soleus muscle
Relative expression of CD11c gene	Before, 1 year and 2 years after the intervention	Relative expression of CD11c gene in biopsied subcutaneous adipose tissue
Relative expression of CD68 gene	Before, 1 year and 2 years after the intervention	Relative expression of CD68 gene in biopsied subcutaneous adipose tissue
Relative expression of MCP1 gene	Before, 1 year and 2 years after the intervention	Relative expression of MCP1 gene in biopsied subcutaneous adipose tissue
Relative expression of IL6 gene	Before, 1 year and 2 years after the intervention	Relative expression of IL6 gene in biopsied subcutaneous adipose tissue
Plasma levels of c-reactive protein	Before, 1 year and 2 years after the intervention	Levels of c-reactive protein in peripheral venous blood
Serum Levels of glucose	Before, 1 month, 3 months, 6 months, 1 year and 2 years after intervention	Levels of glucose in peripheral blood
Serum Levels of glucagon	Before, 1 month, 3 months, 6 months, 1 year and 2 years after intervention	Levels of glucagon in peripheral blood
Serum Levels of GIP	Before, 1 month, 3 months, 6 months, 1 year and 2 years after intervention	Levels of GIP in peripheral blood

Trial Locations

Locations (1)

Neuroendocrine Unit; Columbia University Medical Center, 180 Fort Washington Avenue 9-970; 🇺🇸 New York, New York, United States