Growth Hormone Treatment on Phosphocreatine Recovery in Obesity

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Hideo Makimura, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01421589
First received: August 19, 2011
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

Obesity is associated with reduced growth hormone (GH) secretion. Reduced GH secretion in obesity is associated with increased cardiovascular disease risk. However, it is not yet known how reduced GH increases cardiovascular disease risk in obesity. The investigators hypothesize that reduced GH contributes to dysfunction of the mitochondria. Therefore, the investigators hypothesize that treatment of obese subjects with reduced GH secretion with GH will improve mitochondrial function and that this improvement in mitochondrial function will contribute, in part, to the effects of GH to improve metabolic parameters in obesity. The investigators propose to study skeletal muscle mitochondria in obese subjects with reduced GH secretion using magnetic resonance spectroscopy and muscle biopsies before and after treatment with GH.


Condition Intervention
Obese
Growth Hormone Secretion Abnormality
Drug: Growth hormone treatment

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Effects of Short Term Growth Hormone Treatment on Skeletal Muscle Phosphocreatine Recovery in Obesity

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Phosphocreatine Recovery [ Time Frame: 12-weeks ] [ Designated as safety issue: No ]
    The primary objective of this study is to determine the effects of growth hormone on mitochondrial function as assessed by 31P-MRS in obese subjects with reduced GH secretion. Mitochondrial function was represented by ViPCr, a measure of phosphocreatine recovery after sub-maximal exercise. Univariate regression analyses was performed to assess the relationship between the change in skeletal muscle IGF-1 mRNA after 12 weeks treatment with rhGH to change in ViPCr.


Secondary Outcome Measures:
  • Change in Circulating IGF-1 Concentration [ Time Frame: Baseline and 12-weeks ] [ Designated as safety issue: No ]
    Change in circulating IGF-1 from Baseline to 12-weeks is reported.

  • Change in Skeletal Muscle IGF-1 Gene Expression [ Time Frame: Baseline and 12-weeks ] [ Designated as safety issue: No ]
    Change in skeletal muscle IGF-1 gene mRNA expression from Baseline to 12-weeks is reported.

  • Change in Body Composition [ Time Frame: Baseline and 12-weeks ] [ Designated as safety issue: No ]
    Change in waist circumference from Baseline to 12-weeks is reported.

  • Change in Inflammatory Marker [ Time Frame: Baseline and 12-weeks ] [ Designated as safety issue: No ]
    Change in high sensitivity C-reactive protein (hsCRP) from Baseline to 12-weeks is reported.

  • Change in Insulin Sensitivity [ Time Frame: Baseline and 12-weeks ] [ Designated as safety issue: Yes ]
    Change in fasting glucose from Baseline to 12-weeks is reported.

  • Change in Phosphocreatine Recovery [ Time Frame: Baseline and 12-weeks ] [ Designated as safety issue: No ]
    Change in phosphocreatine recovery, represented by ViPCr, from Baseline to 12-weeks is reported.


Enrollment: 15
Study Start Date: September 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Growth Hormone Drug: Growth hormone treatment
Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men age 18-60 years old
  2. BMI ≥ 30 kg/m2
  3. Waist circumference ≥ 102 cm
  4. Peak GH value of ≤ 4.2 μg/l on standard GHRH-arginine stimulation test

Exclusion Criteria:

  1. Obesity due to a known secondary cause (Cushing's syndrome, hypothyroidism, etc) or a history of gastric bypass procedure.
  2. Subjects who have a known history of diabetes, fasting blood sugar >125 mg/dl or using any anti-diabetic drugs.
  3. Use of Aspirin, Clopidogrel (Plavix), Warfarin (Coumadin) or other anti-coagulants
  4. Subjects on testosterone, glucocorticoids, anabolic steroids, GHRH, GH or IGF-1 within 3 months of enrollment.
  5. Changes in lipid lowering or anti-hypertensive regimen within 3 months of screening
  6. History of pituitary tumor, hypopituitarism, pituitary surgery, pituitary/brain radiation or traumatic brain injury or any other condition known to affect the GH axis.
  7. Severe chronic illness including HIV, active malignancy or history of colon cancer.
  8. Hemoglobin < 9.0 g/dL, SGOT > 2.5 x upper limit normal, Creatinine >1.5 mg/dL, or PSA >5 ng/ml.
  9. Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.
  10. Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient.
  11. Contraindications to MRI scanning.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01421589

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Pfizer
Investigators
Principal Investigator: Hideo Makimura, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Hideo Makimura, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01421589     History of Changes
Other Study ID Numbers: 2011-P-000770
Study First Received: August 19, 2011
Results First Received: March 31, 2014
Last Updated: May 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Growth hormone
GH
Obesity
Mitochondrial function
reduced growth hormone secretion

Additional relevant MeSH terms:
Obesity
Body Weight
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Hormones
Phosphocreatine
Cardiotonic Agents
Cardiovascular Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014