A Prospective Study of Outcome After Therapy for Acromegaly

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acromegaly
• Intervention / Treatment: Procedure: Surgery for acromegaly; Drug: Medications for acromegaly; Diagnostic test: Total body magnetic resonance imaging; Procedure: Adipose Tissue Biopsy

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 Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Neuroendocrine Unit; Columbia University Medical Center, 180 Fort Washington Avenue 9-970

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects newly diagnosed with acromegaly or who have previously undergone surgery for acromegaly are invited to participate.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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: Drugs used to lower growth hormone; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Pamela U Freda, M.D., Columbia University

Publications and helpful links

General Publications

• Freda PU, Reyes-Vidal C, Jin Z, Pugh M, Panigrahi SK, Bruce JN, Wardlaw SL. Plasma Agouti-Related Protein Levels in Acromegaly and Effects of Surgical or Pegvisomant Therapy. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5453-5461. doi: 10.1210/jc.2019-01079.
• Reyes-Vidal CM, Mojahed H, Shen W, Jin Z, Arias-Mendoza F, Fernandez JC, Gallagher D, Bruce JN, Post KD, Freda PU. Adipose Tissue Redistribution and Ectopic Lipid Deposition in Active Acromegaly and Effects of Surgical Treatment. J Clin Endocrinol Metab. 2015 Aug;100(8):2946-55. doi: 10.1210/jc.2015-1917. Epub 2015 Jun 2.
• Reyes-Vidal C, Fernandez JC, Bruce JN, Crisman C, Conwell IM, Kostadinov J, Geer EB, Post KD, Freda PU. Prospective study of surgical treatment of acromegaly: effects on ghrelin, weight, adiposity, and markers of CV risk. J Clin Endocrinol Metab. 2014 Nov;99(11):4124-32. doi: 10.1210/jc.2014-2259. Epub 2014 Aug 19.

Helpful Links

• Columbia University Medical Center: Neuroendocrine Diseases Program

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2003
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: August 8, 2012
• First Submitted That Met QC Criteria: March 11, 2013
• First Posted (Estimate): March 13, 2013

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Acromegaly; Pituitary tumor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Acromegaly; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: AAAA0890; R56DK064720 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No