Growth Hormone Treatment on Phosphocreatine Recovery in Obesity

The Effects of Short Term Growth Hormone Treatment on Skeletal Muscle Phosphocreatine Recovery in Obesity

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.

Study Overview

• Status: Completed
• Conditions: Obese; Growth Hormone Secretion Abnormality
• Intervention / Treatment: Drug: Growth hormone treatment

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phosphocreatine Recovery	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.	12-weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Circulating IGF-1 Concentration	Change in circulating IGF-1 from Baseline to 12-weeks is reported.	Baseline and 12-weeks
Change in Skeletal Muscle IGF-1 Gene Expression	Change in skeletal muscle IGF-1 gene mRNA expression from Baseline to 12-weeks is reported.	Baseline and 12-weeks
Change in Body Composition	Change in waist circumference from Baseline to 12-weeks is reported.	Baseline and 12-weeks
Change in Inflammatory Marker	Change in high sensitivity C-reactive protein (hsCRP) from Baseline to 12-weeks is reported.	Baseline and 12-weeks
Change in Insulin Sensitivity	Change in fasting glucose from Baseline to 12-weeks is reported.	Baseline and 12-weeks
Change in Phosphocreatine Recovery	Change in phosphocreatine recovery, represented by ViPCr, from Baseline to 12-weeks is reported.	Baseline and 12-weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: August 22, 2011
• First Posted (Estimate): August 23, 2011

Study Record Updates

• Last Update Posted (Estimate): July 1, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Obesity; Growth hormone; Mitochondrial function; GH; reduced growth hormone secretion
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2011-P-000770