Brief Title
Adipose Tissue and Serum Inflammation in GH Deficiency
Official Title
Adipose Tissue and Serum Inflammation in Growth Hormone (GH) Deficiency
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 Type
Observational
Primary Outcome
Visceral Adipose Tissue (VAT) mass
Secondary Outcome
Intra-hepatic lipid level
Condition
Growth Hormone Deficiency
Intervention
Growth Hormone
Study Arms / Comparison Groups
Adults with growth hormone deficiency
Description: 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.
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
60
Start Date
May 19, 2019
Completion Date
April 2022
Primary Completion Date
April 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
growth hormone response < 3 ng/ml or 3 or more pituitary hormone deficiencies and
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 growth hormone 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 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
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
NCT03500913
Organization ID
AAAP3950
Secondary IDs
1R01DK110771-01A1
Responsible Party
Principal Investigator
Study Sponsor
Columbia University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study Sponsor
Pamela U. Freda, MD, Principal Investigator, Columbia University
Verification Date
July 2021