Brief Title
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
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.
Study Type
Observational
Primary Outcome
Relative gene expression values of CD68 gene
Secondary Outcome
Relative gene expression IL6 gene
Condition
Growth Hormone Deficiency
Intervention
Growth hormone
Study Arms / Comparison Groups
Adults with growth hormone deficiency
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
12
Start Date
August 1, 2017
Completion Date
July 30, 2022
Primary Completion Date
July 30, 2022
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
Gender
All
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Pamela U. Freda, MD, 212-305-4921, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03225755
Organization ID
AAAR3797
Responsible Party
Principal Investigator
Study Sponsor
Columbia University
Collaborators
Novo Nordisk A/S
Study Sponsor
Pamela U. Freda, MD, Principal Investigator, Columbia University
Verification Date
July 2021