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

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ClinicalTrials.gov Identifier: NCT03225755
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : February 19, 2019
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Pamela U. Freda, Columbia University

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.

Condition or disease Intervention/treatment
Growth Hormone Deficiency Drug: Growth hormone

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.

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Study Type : Observational
Estimated Enrollment : 12 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Adipose Tissue and Circulating Markers of Inflammation in GH Deficiency and Changes With GH Therapy
Actual Study Start Date : August 1, 2017
Estimated Primary Completion Date : July 30, 2019
Estimated Study Completion Date : July 30, 2019


Group/Cohort Intervention/treatment
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
Patients will receive growth hormone replacement therapy as per standard clinical care during this study.




Primary Outcome Measures :
  1. Relative gene expression values of CD68 gene [ Time Frame: Baseline to 12 months of GH therapy ]
    Relative gene expression values of cluster of differentiation (CD68) gene in adipose tissue


Secondary Outcome Measures :
  1. Relative gene expression IL6 gene [ Time Frame: Baseline to 12 months of GH therapy ]
    Relative gene expression interleukin 6 (IL6) gene in adipose tissue

  2. Relative gene expression values of MCP1 gene [ Time Frame: Baseline to 12 months of GH therapy ]
    Relative gene expression values of monocyte chemoattractant protein-1 (MCP1) gene in adipose tissue

  3. Relative gene expression values of CD11c gene [ Time Frame: Baseline to 12 months of GH therapy ]
    Relative gene expression values of CD11c gene in adipose tissue

  4. Visceral Adipose Tissue (VAT) mass [ Time Frame: Baseline to 12 months of GH therapy ]
    Visceral Adipose Tissue (VAT) mass as measured by magnetic resonance imaging of abdomen

  5. Intra-hepatic lipid level [ Time Frame: Baseline to 12 months of GH therapy ]
    Intra-hepatic lipid level measured by magnetic resonance imaging of liver

  6. Resting metabolic rate [ Time Frame: Baseline to 12 months of GH therapy ]
    Resting metabolic rate

  7. Interleukin 6 (IL-6) level [ Time Frame: Baseline to 12 months of GH therapy ]
    Plasma level of interleukin 6 (IL-6)

  8. TNFα level [ Time Frame: Baseline to 12 months of GH therapy ]
    Plasma level of tumor necrosis factor alpha (TNFα)

  9. C-reactive protein level [ Time Frame: Baseline to 12 months of GH therapy ]
    Plasma level of c-reactive protein (CRP)

  10. Homocysteine level [ Time Frame: Baseline to 12 months of GH therapy ]
    Plasma level of homocysteine


Biospecimen Retention:   Samples Without DNA
  1. Peripheral venous blood
  2. Subcutaneous adipose tissue


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03225755


Contacts
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Contact: Carlos Reyes-Vidal, MD 212-305-4921 csr52@columbia.edu
Contact: Pamela Freda, MD 212-305-2254

Locations
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United States, New York
Neuroendocrine Unit and Pituitary Center, Columbia University Recruiting
New York, New York, United States, 10032
Contact: Pamela U. Freda, MD    212-305-2254      
Contact: Carlos M. Reyes-Vidal, MD    212-305-4921    csr52@cumc.columbia.edu   
Sponsors and Collaborators
Columbia University
Novo Nordisk A/S
Investigators
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Principal Investigator: Pamela U. Freda, MD Columbia University

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Responsible Party: Pamela U. Freda, Professor of Medicine at CUMC, Columbia University
ClinicalTrials.gov Identifier: NCT03225755     History of Changes
Other Study ID Numbers: AAAR3797
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Pamela U. Freda, Columbia University:
Growth Hormone Deficiency
Adipose Tissue
Inflammation

Additional relevant MeSH terms:
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Dwarfism, Pituitary
Dwarfism
Inflammation
Endocrine System Diseases
Pathologic Processes
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs