Clinical trial NCT03225755: Adipose Tissue and Circulating Markers of Inflammation in GH Deficiency and Changes With GH Therapy
Official title: Adipose Tissue and Circulating Markers of Inflammation in GH Deficiency and Changes With GH Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Growth Hormone Deficiency
Keywords: Growth Hormone Deficiency
Adipose Tissue
Inflammation
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2017-07-21
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: The growth hormone (GH) axis has important influences on adipose tissue. GH may have a novel effect to reduce macrophage yet increase adipocyte inflammation in adipose tissue along with reducing adipose tissue mass. Disordered adipose tissue metabolism may dysregulate adipokine secretion, which could contribute to metabolic abnormalities in GH deficiency. Adipokines, peptides expressed and secreted by adipose tissue, exert important local adipose tissue and systemic metabolic effects. This study will combine direct assessment of adipose tissue with assessment of body composition. Adult GHD can be associated with central adiposity, insulin resistance, dyslipidemia and increased cardiovascular (CV) risk.

Eligibility criteria: Inclusion criteria:

1. 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.
2. 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
3. No history of diabetes mellitus and fasting blood sugar at screening visit ≤ 120 mg/dl.
4. 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.
5. May have a history of radiotherapy, but they must have completed their course of radiotherapy more than 3 months prior to study screening.
6. If prior GH therapy must have not received prior GH replacement therapy in 310 the 6 months prior to screening.
7. 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.
8. 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.
9. 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.

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 GH 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

Primary outcomes:
measure: Relative gene expression values of CD68 gene
timeFrame: Baseline to 12 months of GH therapy
Secondary outcomes:
measure: Relative gene expression IL6 gene
timeFrame: Baseline to 12 months of GH therapy
measure: Relative gene expression values of MCP1 gene
timeFrame: Baseline to 12 months of GH therapy
measure: Relative gene expression values of CD11c gene
timeFrame: Baseline to 12 months of GH therapy
measure: Visceral Adipose Tissue (VAT) mass
timeFrame: Baseline to 12 months of GH therapy
measure: Intra-hepatic lipid level
timeFrame: Baseline to 12 months of GH therapy
measure: Resting metabolic rate
timeFrame: Baseline to 12 months of GH therapy
measure: Interleukin 6 (IL-6) level
timeFrame: Baseline to 12 months of GH therapy
measure: TNFα level
timeFrame: Baseline to 12 months of GH therapy
measure: C-reactive protein level
timeFrame: Baseline to 12 months of GH therapy
measure: Homocysteine level
timeFrame: Baseline to 12 months of GH therapy
Other outcomes:
Locations:
city: New York
country: United States
facility: Neuroendocrine Unit and Pituitary Center, Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: Pamela U. Freda, MD
role: PRINCIPAL_INVESTIGATOR
References: