Adipose Tissue and Serum Inflammation in GH Deficiency

Completed

• Conditions: Growth Hormone Deficiency
• Interventions: Drug: Growth Hormone

• Registration Number: NCT03500913
• Lead Sponsor: Columbia University

Brief Summary

This study will examine adipose tissue inflammation and adipokine expression and serum markers of inflammation and adipokine levels in patients with growth hormone (GH) deficiency before and after treatment.

Detailed Description

The GH axis has important influences on adipose tissue. Preliminary data from the investigators' study in acromegaly, a state of GH excess, suggests that GH reduces adipose tissue (AT) mass and serum inflammation. However, GH seems to reduce macrophage markers in adipose tissue yet increase adipocyte inflammation. This novel dissociation of macrophage and adipocyte inflammation is hypothesized to be due to GH. In order to examine this hypothesis further this study will examine adipose tissue and serum inflammation in patients with GH deficiency before and after GH therapy. The investigators will obtain subcutaneous adipose tissue by biopsy in patients with active GH deficiency planning to undergo therapy for GH deficiency. Concurrently serum samples will be taken for analysis of levels of inflammatory markers and adipokines. After treatment for 12 months with a normal levels of Insulin-like growth factor 1 (IGF-1), a marker of GH deficiency, patients will have a repeat adipose tissue biopsy. Adipose tissue parameters will be analyzed in each specimen and then compared to each patient over time as well as to body mass index (BMI)-matched control subjects.

Study Timeline

• Study First Submitted: 2018-04-10
• Study First Submitted QC: 2018-04-10
• Study First Posted: 2018-04-18
• Study Start: 2019-05-19
• Primary Completion: 2020-02-12
• Study Completion: 2020-02-20
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-08
• Last Update Posted: 2025-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

1. Have other conditions that may result in abnormal GH and/or IGF-I concentrations (e.g., severe hepatic disease, severe renal disease, malnutrition, treatment with levodopa).
2. Alanine aminotransferase (ALT) or aspartate transaminase (AST) ≥ 2 x upper limit of normal or clinically significant hepatic disease or renal impairment defined as creatinine > 1.5x upper normal.
3. Have a pituitary adenoma with a distance to the optic chiasm of 5 mm or less, confirmed by a recent MRI scan (within two months prior to the screening visit).
4. Pituitary tumor growth within the 12 months prior to study entry.
5. GH therapy within 6 months of screening.
6. Diabetes mellitus.
7. History of acromegaly.
8. History of active Cushing's disease within 24 months of screening
9. Visual field defects or other neurological symptoms due to current tumor mass compression.
10. Have known or suspected drug or alcohol abuse.
11. Have received an investigational medication within four weeks prior to Screening or is scheduled to receive any investigational medication during the study.
12. Do not have the ability to fully comprehend the nature of the study, to follow instructions, cooperate with study procedures, and/or are unable to adhere to the visit scheduled outlined in the protocol.
13. Have other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
14. History of a malignancy other than squamous or basal cell skin carcinoma that has been excised or intracranial malignant tumors or leukemia within 5 years of screening.
15. Patients who have a known hypersensitivity to growth hormone therapy
16. Use of weight 349 loss medications
17. Females who plan to change estrogen therapy during the trial
18. Patients who have received supraphysiologic doses of glucocorticoids within the past 6 months (except for peri-operative (< 3 days duration) of dexamethasone), or who are currently receiving any chemotherapeutic agents.
19. Patients who have received other investigational drugs administered or received within 30 days of study entry

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Adults with growth hormone deficiency	Growth Hormone	Subjects who present to the neuroendocrine unit at Columbia University Irving Medical Center (CUIMC) for therapy of GH deficiency or who are followed in the unit and have active GH deficiency and are planning to initiate a therapy.

Primary Outcome Measures

Name	Time	Method
Visceral Adipose Tissue (VAT) mass	Baseline to 12 months of GH therapy	Visceral adipose tissue mass as measured by tota body magnetic resonance imaging

Secondary Outcome Measures

Name	Time	Method
Relative gene expression values of MCP1 gene	Baseline to 12 months of GH therapy	Relative gene expression values of monocyte chemoattractant protein-1 (MCP-1) gene in adipose tissue
Total body fat	Baseline to 12 months of GH therapy	Total body fat as measured by dual x-ray absorptiometry
Relative gene expression IL6 gene	Baseline to after 12 months of treatment for GH deficiency	Relative gene expression Interleukin 6 (IL6) gene in adipose tissue
Relative gene expression of CD68 gene	Baseline to 12 months of GH therapy	Relative gene expression values of Cluster of Differentiation 68 (CD68) gene expression in adipose tissue
TNFα level	Baseline to 12 months of GH therapy	Plasma level of tumor necrosis factor alpha (TNFα)
Intra-hepatic lipid level	Baseline to 12 months of GH therapy	Intra-hepatic lipid level measured by magnetic resonance imaging of liver
Skeletal Muscle Mass	Baseline to 12 months of GH therapy	Skeletal muscle mass measured by total body magnetic resonance imaging
Resting metabolic rate	Baseline to 12 months of GH therapy	Resting metabolic rate
homocysteine level	Baseline to 12 months of GH therapy	Plasma level of homocysteine
Relative gene expression values of CD11c gene	Baseline to 12 months of GH therapy	Relative gene expression values of CD11c gene in adipose tissue
interleukin 6 (IL-6) level	Baseline to 12 months of GH therapy	Plasma level of interleukin 6 (IL-6)
CRP level	Baseline to 12 months of GH therapy	Plasma level of C-reactive protein (CRP)

Trial Locations

Locations (1)

Neuroendocrine Unit and Pituitary Center, Columbia University Irving Medical Center; 🇺🇸 New York, New York, United States