A Prospective Study of Outcome After Therapy for Acromegaly
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Acromegaly Subjects 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
(non-experimental) standard procedure
Drug: Medications for acromegaly
(non-experimental) standard procedure
Other Names:
Diagnostic Test: Total body magnetic resonance imaging
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.
Procedure: Adipose Tissue Biopsy
Subjects will undergo biopsy of subcutaneous adipose tissue before and 12 and 24 months after surgery or medical therapy for acromegaly.
|
| Healthy Subjects 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
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.
Procedure: Adipose Tissue Biopsy
Subjects will undergo biopsy of subcutaneous adipose tissue before and 12 and 24 months after surgery or medical therapy for acromegaly.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- 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
- 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
Eligibility Criteria
Criteria
Acromegaly Subjects
Inclusion Criteria:
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Adult males and females.
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Ages 18 and over.
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Presenting to the PI or one of the sub-investigators for evaluation of acromegaly.
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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.
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Willingness to participate in this study's procedures.
Exclusion Criteria:
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Subjects who are unwilling to comply with the procedures outlined in the study.
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Subjects who do not have the ability to fully comprehend the nature of the study, to follow instructions, and/or cooperate with study procedures
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Are unwilling to provide informed consent to participate in the study.
Healthy Subjects
Inclusion Criteria:
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Adult males and females.
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Ages 18 and over.
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Responding to ads for participation or by word of mount.
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No medical problems, no medications, stable weight for 3 months prior to study.
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Willingness to participate in this study's procedures.
Exclusion Criteria:
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Subjects who are unwilling to comply with the procedures outlined in the study.
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Subjects who do not have the ability to fully comprehend the nature of the study, to follow instructions, and/or cooperate with study procedures
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Are unwilling to provide informed consent to participate in the study.
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Failure to meet the inclusion criteria.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Neuroendocrine Unit; Columbia University Medical Center, 180 Fort Washington Avenue 9-970 | New York | New York | United States | 10032 |
Sponsors and Collaborators
- Columbia University
- Icahn School of Medicine at Mount Sinai
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Pamela U Freda, M.D., Columbia University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- AAAA0890
- R56DK064720