Adipose Tissue and Circulating Markers of Inflammation in GH Deficiency and Changes With GH Therapy

NCT03225755 | Completed FDA Drug

• 1 other identifier: AAAR3797
• Study Type: observational
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

In order to examine the effect of GH on adipose tissue inflammation, this study will examine adipose tissue and serum inflammation in patients with GH deficiency before and after GH therapy. The investigators will also obtain serum samples before and after treatment for adipokines, inflammatory markers and examine macrophages in circulation with regard to their inflammatory state. The investigators will also obtain adipose tissue biopsies from healthy subjects matched to the growth hormone deficiency (GHD) subjects. Adipose tissue specimens will be analyzed for adipose tissue morphology, adipocyte size, adipokine gene expression, and adipose tissue macrophage number.

Conditions

Growth Hormone Deficiency

Keywords

Growth Hormone Deficiency; Adipose Tissue; Inflammation

Outcome Measures

Primary Outcomes (1)

• Relative gene expression values of CD68 gene

  Relative gene expression values of cluster of differentiation (CD68) gene in adipose tissue

  Baseline to 12 months of GH therapy

Secondary Outcomes (10)

• Relative gene expression IL6 gene

  Baseline to 12 months of GH therapy

• Relative gene expression values of MCP1 gene

  Baseline to 12 months of GH therapy

• Relative gene expression values of CD11c gene

  Baseline to 12 months of GH therapy

• Visceral Adipose Tissue (VAT) mass

  Baseline to 12 months of GH therapy

• Intra-hepatic lipid level

  Baseline to 12 months of GH therapy

Study Arms (1)

Adults with growth hormone deficiency

12 subjects with GH deficiency, adult or childhood onset, and not currently on GH therapy will be studied. Subjects enrolled will be those planning GH therapy and beginning this therapy as part of their routine clinical care. Subjects will be 50% female and all subjects will be on 3 months of stable hormone replacements prior to testing.

Drug: Growth hormone

Interventions

Growth hormone DRUG

Patients will receive growth hormone replacement therapy as per standard clinical care during this study.

Adults with growth hormone deficiency

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Potential subjects include all those who present to our Neuroendocrine Unit for therapy of GH deficiency or who are followed in our unit and have GH deficiency and are planning to initiate a therapy. Subjects will be those with central adiposity. We expect are study group to be approximately half women and reflect the ethnic mix of our study populations of our other pituitary tumor studies, which is primarily drawn from the New York Metropolitan area.

You may qualify if:

• Males or females age ≥18 years with diagnosis of GH deficiency that is Adult Onset, either alone or associated with multiple pituitary hormone deficiencies and due to pituitary disease,hypothalamic disease, surgery, radiation therapy or Childhood Onset due to congenital, genetic, acquired, or idiopathic causes.
• Diagnosis of GH deficiency defined by: insulin tolerance test or glucagon test: peak GH response \< 3 ng/ml or 3 or more pituitary hormone deficiencies and insulin-like growth factor 1 (IGF-1) standard deviation score \< -2.0
• No history of diabetes mellitus and fasting blood sugar at screening visit ≤ 120 mg/dl.
• If patients have undergone surgical resection of a pituitary adenoma, a minimum of 12 months must have elapsed post surgery prior to enrollment and tumor will be demonstrated to be unchanged for 12 months or longer since surgery.
• May have a history of radiotherapy, but they must have completed their course of radiotherapy more than 3 months prior to study screening.
• If prior GH therapy must have not received prior GH replacement therapy in 310 the 6 months prior to screening.
• Stable pituitary hormone supplements (x 3 months) prior to baseline visit and normal levels of free thyroxine, testosterone in males and normal adrenal function if not on replacement therapy.
• If female, a. Not pregnant (as evidenced by a negative serum pregnancy test) or lactating and b. If of childbearing potential, agrees to use a medically acceptable form of contraception (such as oral, implantable, or barrier contraception) from the time of screening, for the duration of the study, and for at least one month after study discontinuation or completion. Childbearing potential is defined as women who are not surgically sterile or not at least one year postmenopausal.
• Sign and date an informed consent document indicating that the subject (or legally acceptable representative) has been informed of and agrees to all pertinent aspects of the trial.

You may not qualify if:

• 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).
• 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.
• 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).
• Pituitary tumor growth within the 12 months prior to study entry.
• GH therapy within 6 months of screening.
• Diabetes mellitus.
• History of acromegaly.
• History of active Cushing's disease within 24 months of screening
• Visual field defects or other neurological symptoms due to current tumor mass compression.
• Have known or suspected drug or alcohol abuse.
• Have received an investigational medication within four weeks prior to Screening or is scheduled to receive any investigational medication during the study.
• 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.
• 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.
• 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.
• Patients who have a known hypersensitivity to GH therapy

Sponsors & Collaborators

• Columbia University: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Neuroendocrine Unit and Pituitary Center, Columbia University

New York, New York, 10032, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

1. Peripheral venous blood 2. Subcutaneous adipose tissue

MeSH Terms

Conditions

Dwarfism, Pituitary; Inflammation

Interventions

Growth Hormone

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Pamela U. Freda, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine at CUMC

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: July 21, 2017
• Study Start: August 1, 2017
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: May 13, 2025

Record last verified: 2025-05

Locations

US (1)