A Prospective Study of Outcome After Therapy for Acromegaly

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective Study of Outcome After Therapy for Acromegaly

Conditions
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Acromegaly

Intervention / Treatment
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* Procedure: Surgery for acromegaly
* Drug: Medications for acromegaly
* Diagnostic Test: Total body magnetic resonance imaging
* Procedure: Adipose Tissue Biopsy


Participation Criteria
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Eligibility Criteria
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Acromegaly Subjects 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acromegaly Subjects<br>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. | Procedure: Surgery for acromegaly<br>* (non-experimental) standard procedure<br>Drug: Medications for acromegaly<br>* (non-experimental) standard procedure<br>* Other names: Drugs used to lower growth hormone;Diagnostic Test: Total body magnetic resonance imaging<br>* Subjects will undergo total body MRI with spectroscopy of the muscle and liver before and 3-6 months, 12 and 24 months after surgery or medical therapy for acromegaly.<br>Procedure: Adipose Tissue Biopsy<br>* Subjects will undergo biopsy of subcutaneous adipose tissue before and 12 and 24 months after surgery or medical therapy for acromegaly.<br>|
| Healthy Subjects<br>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. | Diagnostic Test: Total body magnetic resonance imaging<br>* Subjects will undergo total body MRI with spectroscopy of the muscle and liver before and 3-6 months, 12 and 24 months after surgery or medical therapy for acromegaly.<br>Procedure: Adipose Tissue Biopsy<br>* Subjects will undergo biopsy of subcutaneous adipose tissue before and 12 and 24 months after surgery or medical therapy for acromegaly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical activity of 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. | At 5 years after therapy for acromegaly | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acromegaly, Pituitary tumor