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Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

Primary Purpose

NAFLD

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

somatropin

About this trial

This is an interventional treatment trial for NAFLD focused on measuring obesity, adolescence, fatty liver, growth hormone

Eligibility Criteria

18 Years - 29 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Males and Females ages 18-29yo
BMI ≥95th percentile and/or ≥30kg/m^2
Hepatic fat ≥5% by hydrogen magnetic resonance spectroscopy (1H-MRS)
IGF-1 standard deviation score (SDS) < 0

Exclusion criteria:

Alcohol consumption of >14 drinks per week (Females) or >21 drinks per week (Males)
Use of insulin or oral anti-diabetic medications, or hemoglobin A1c (HbA1c) >7% or fasting glucose ≥126mg/dL
Use of corticosteroid, gonadal steroids, or methotrexate ≤ 3 months prior to baseline visit
Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis
hemoglobin < 11.0 g/dL or weight < 50kg
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x upper limit of normal (ULN), total bilirubin > ULN, positive hepatitis B surface antigen (sAg), or positive hepatitis C antibody
Routine magnetic resonance imaging (MRI) exclusion criteria (including weight >450 pounds)
Use of weight-loss medications or previous weight loss surgery
Pregnant or breastfeeding, or, for sexually-active females, unwillingness to use an appropriate form of contraception during the study
Known cirrhosis or clinical evidence of cirrhosis or portal hypertension on imaging or exam
Use of growth hormone (GH) or growth hormone releasing hormone within the past 1 year
Change in lipid lowering or anti-hypertensive medications within 3 months of screening
Change in vitamin E or ursodiol <6 months before screen; subjects on stable doses of Vitamin E and/or Ursodiol for ≥6 months will be eligible.
History of malignancy or active malignancy
History of hypopituitarism, head irradiation or any other condition or chronic illness known to affect the GH axis

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Growth hormone

No treatment

Arm Description

Somatropin given by daily subcutaneous injection. Dose will begin at 1mg and be titrated based on insulin-like growth factor 1 (IGF-1) levels.

(no study treatment - observation only)

Outcomes

Primary Outcome Measures

Change in Hepatic Fat Fraction

change in hepatic fat fraction between baseline and 24 weeks as measured by hydrogen magnetic resonance spectroscopy

Secondary Outcome Measures

Change in Aspartate Aminotransferase (AST)

change in AST between baseline and 24 weeks

Change in Alanine Aminotransferase (ALT)

change in ALT between baseline and 24 weeks

Change in Gamma Glutamyl Transferase (GGT)

change in GGT between baseline and 24 weeks

Change in Visceral Adipose Tissue

Change in visceral adipose tissue cross-sectional area at the 4th lumbar vertebra as measured by magnetic resonance imaging between baseline and 24 weeks

Full Information

NCT ID

NCT02726542

First Posted

March 30, 2016

Last Updated

August 11, 2022

Sponsor

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02726542

Brief Title

Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

Official Title

Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

May 3, 2017 (Actual)

Primary Completion Date

April 2, 2020 (Actual)

Study Completion Date

April 2, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Fatty liver disease is an increasing problem in overweight and obese young adults. The purpose of this study is to test the effect of growth hormone on liver fat in obese young adults ages 18-29y with increased liver fat.

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) is a significant health problem in obese adolescents. Obese children and adolescents have significant reductions in growth hormone secretion, and we hypothesize that augmenting growth hormone in this population will decrease liver fat. Growth hormone inhibits hepatic de novo lipogenesis, which is an important source of hepatic lipid. Patients with pituitary GH deficiency have a higher prevalence of NAFLD and non-alcoholic steatohepatitis (NASH) than the general population, and replacement of GH in these individuals reduces signs of liver damage. The purpose of this study is to test the hypothesis that growth hormone treatment will decrease liver fat quantity in young adults who begin the trial with more than 5% liver fat measured by magnetic resonance spectroscopy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

NAFLD

Keywords

obesity, adolescence, fatty liver, growth hormone

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Growth hormone

Arm Type

Experimental

Arm Description

Somatropin given by daily subcutaneous injection. Dose will begin at 1mg and be titrated based on insulin-like growth factor 1 (IGF-1) levels.

Arm Title

No treatment

Arm Type

No Intervention

Arm Description

(no study treatment - observation only)

Intervention Type

Drug

Intervention Name(s)

somatropin

Intervention Description

Norditropin (growth hormone) given by injection using a pen-device

Primary Outcome Measure Information:

Title

Change in Hepatic Fat Fraction

Description

change in hepatic fat fraction between baseline and 24 weeks as measured by hydrogen magnetic resonance spectroscopy

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Change in Aspartate Aminotransferase (AST)

Description

change in AST between baseline and 24 weeks

Time Frame

24 weeks

Title

Change in Alanine Aminotransferase (ALT)

Description

change in ALT between baseline and 24 weeks

Time Frame

24 weeks

Title

Change in Gamma Glutamyl Transferase (GGT)

Description

change in GGT between baseline and 24 weeks

Time Frame

24 weeks

Title

Change in Visceral Adipose Tissue

Description

Change in visceral adipose tissue cross-sectional area at the 4th lumbar vertebra as measured by magnetic resonance imaging between baseline and 24 weeks

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

29 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Males and Females ages 18-29yo BMI ≥95th percentile and/or ≥30kg/m^2 Hepatic fat ≥5% by hydrogen magnetic resonance spectroscopy (1H-MRS) IGF-1 standard deviation score (SDS) < 0 Exclusion criteria: Alcohol consumption of >14 drinks per week (Females) or >21 drinks per week (Males) Use of insulin or oral anti-diabetic medications, or hemoglobin A1c (HbA1c) >7% or fasting glucose ≥126mg/dL Use of corticosteroid, gonadal steroids, or methotrexate ≤ 3 months prior to baseline visit Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis hemoglobin < 11.0 g/dL or weight < 50kg aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x upper limit of normal (ULN), total bilirubin > ULN, positive hepatitis B surface antigen (sAg), or positive hepatitis C antibody Routine magnetic resonance imaging (MRI) exclusion criteria (including weight >450 pounds) Use of weight-loss medications or previous weight loss surgery Pregnant or breastfeeding, or, for sexually-active females, unwillingness to use an appropriate form of contraception during the study Known cirrhosis or clinical evidence of cirrhosis or portal hypertension on imaging or exam Use of growth hormone (GH) or growth hormone releasing hormone within the past 1 year Change in lipid lowering or anti-hypertensive medications within 3 months of screening Change in vitamin E or ursodiol <6 months before screen; subjects on stable doses of Vitamin E and/or Ursodiol for ≥6 months will be eligible. History of malignancy or active malignancy History of hypopituitarism, head irradiation or any other condition or chronic illness known to affect the GH axis

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Takara Stanley, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

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