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

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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