Growth Hormone and Intrahepatic Lipid Content in Patients With Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of alcohol use, is an increasingly recognized complication of obesity, with prevalence estimates of about 30% of individuals in the United States. A subset of these will develop progressive disease in the form of nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver failure. NAFLD is expected to be the most common indication for liver transplantation by the year 2020. We hypothesize that growth hormone (GH) replacement will decrease intrahepatic lipid accumulation as quantified by 1H magnetic resonance spectroscopy (1H-MRS).

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Fatty Liver Disease (NAFLD)
• Intervention / Treatment: Drug: Growth hormone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 2

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 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ages 18 - 65 yr
2. NAFLD defined as demonstration of hepatic steatosis by imaging or biopsy in absence of significant alcohol consumption and other causes of hepatic steatosis. If liver imaging or biopsy has not been performed clinically, liver ultrasound will be performed as part of the screening visit.

Exclusion Criteria:

1. Serum creatinine > 2 times the upper limit of normal
2. History of cancer, except for non-melanoma skin cancers
3. Active carpel tunnel syndrome
4. Diabetes mellitus, defined as a hemoglobin A1C >6.5 or use of any medications prescribed to treat hyperglycemia. The exception is that the use of metformin is acceptable in patients whose HbA1c has been =<6.0 on two visits and whose weight has remained stable for six months.
5. Contraindications to magnetic resonance imaging (MRI).
6. Pregnancy or desire to become pregnant. Participants of reproductive age must agree to use contraception.
7. Breastfeeding
8. Aspartate and aminotransferase levels >10x upper limit of normal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Growth hormone; Growth hormone (somatropin) administered by daily injection at starting dose of 0.3 mg daily for women and 0.2 mg daily for men, with dose titration for goal IGF-1 in the upper quartile of normal for age.	Drug: Growth hormone; growth hormone, Genotropin (Pfizer); Other Names: Genotropin (Pfizer Inc.)
Placebo Comparator: Placebo; Placebo will be administered by daily injection in this double blind study design. Sham dosing will be performed to maintain blinding.	Drug: Placebo; placebo with identical drug pen delivery device and packaging as Genotropin (Pfizer)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Intrahepatic Lipid Content Between Baseline and 6 Months as Measured by 1H-magnetic Resonance Spectroscopy (1H-MRS). Endpoints Were Assessed at Baseline and 6 Months.	Change in Intrahepatic lipid content by 1H-MRS over 6 months in the GH vs placebo group	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum High Sensitivity C-reactive Protein (hsCRP) Between Baseline and 6 Months.	Change in serum high sensitivity C-reactive protein (hsCRP) (mg/L) between baseline and 6 months.	6 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Karen K Miller, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2017
• Primary Completion (Actual): August 10, 2021
• Study Completion (Actual): September 13, 2021

Study Registration Dates

• First Submitted: July 15, 2014
• First Submitted That Met QC Criteria: August 13, 2014
• First Posted (Estimate): August 15, 2014

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: October 28, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 2014P001680

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No