Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02726542
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 35
• Patients Per Site Per Month: 0.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
NAFLD	Drug: somatropin	Early Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Augmenting Growth Hormone to Ameliorate Nonalcoholic Fatty Liver Disease in Adolescents
• Actual Study Start Date: May 3, 2017
• Actual Primary Completion Date: Apr 2, 2020
• Actual Study Completion Date: Apr 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Growth hormone Somatropin given by daily subcutaneous injection. Dose will begin at 1mg and be titrated based on insulin-like growth factor 1 (IGF-1) levels.	Drug: somatropin; Norditropin (growth hormone) given by injection using a pen-device
No Intervention: No treatment (no study treatment - observation only)

Outcome Measures

Primary Outcome Measures

1. Change in Hepatic Fat Fraction [24 weeks]

   change in hepatic fat fraction as measured by hydrogen magnetic resonance spectroscopy

Secondary Outcome Measures

1. Change in Aspartate Aminotransferase (AST) [24 weeks]

2. Change in Alanine Aminotransferase (ALT) [24 weeks]

3. Change in Gamma Glutamyl Transferase [24 weeks]

4. Change in Visceral Adipose Tissue [24 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 29 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Males and Females ages 18-29yo

2. BMI ≥95th percentile and/or ≥30kg/m^2

3. Hepatic fat ≥5% by hydrogen magnetic resonance spectroscopy (1H-MRS)

4. IGF-1 standard deviation score (SDS) < 0

Exclusion criteria:

1. Alcohol consumption of >14 drinks per week (Females) or >21 drinks per week (Males)

2. Use of insulin or oral anti-diabetic medications, or hemoglobin A1c (HbA1c) >7% or fasting glucose ≥126mg/dL

3. Use of corticosteroid, gonadal steroids, or methotrexate ≤ 3 months prior to baseline visit

4. Known diagnosis of alpha-1 antitrypsin deficiency, Wilson's disease, hemochromatosis, or autoimmune hepatitis

5. hemoglobin < 11.0 g/dL or weight < 50kg

6. 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

7. Routine magnetic resonance imaging (MRI) exclusion criteria (including weight >450 pounds)

8. Use of weight-loss medications or previous weight loss surgery

9. Pregnant or breastfeeding, or, for sexually-active females, unwillingness to use an appropriate form of contraception during the study

10. Known cirrhosis or clinical evidence of cirrhosis or portal hypertension on imaging or exam

11. Use of growth hormone (GH) or growth hormone releasing hormone within the past 1 year

12. Change in lipid lowering or anti-hypertensive medications within 3 months of screening

13. 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.

14. History of malignancy or active malignancy

15. History of hypopituitarism, head irradiation or any other condition or chronic illness known to affect the GH axis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Takara Stanley, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 31, 2019

More Information

Publications

None provided.

• Responsible Party: Takara Stanley, Assistant Professor of Pediatrics, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02726542
• Other Study ID Numbers: 2016p-000657
• First Posted: Apr 1, 2016
• Last Update Posted: Apr 26, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takara Stanley, Assistant Professor of Pediatrics, Massachusetts General Hospital: obesity; adolescence; fatty liver; growth hormone
• Additional relevant MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease

Study Results

Participant Flow

Arm/Group Title	Growth Hormone	No Treatment
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device	(no study treatment - observation only)
Period Title: Overall Study
STARTED	13	11
COMPLETED	10	10
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Growth Hormone	No Treatment	Total
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device	(no study treatment - observation only)	Total of all reporting groups
Overall Participants	13	11	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25 (3)	23 (4)	24 (4)
Sex: Female, Male (Count of Participants)
Female	7 53.8%	6 54.5%	13 54.2%
Male	6 46.2%	5 45.5%	11 45.8%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaskan Native	1 7.7%	0 0%	1 4.2%
Asian	1 7.7%	1 9.1%	2 8.3%
White	9 69.2%	6 54.5%	15 62.5%
Other or more than 1 race	2 15.4%	4 36.4%	6 25%
Hispanic (independent of race)	4 30.8%	4 36.4%	8 33.3%
Region of Enrollment (participants) [Number]
United States	13 100%	11 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Change in Hepatic Fat Fraction
Description	change in hepatic fat fraction as measured by hydrogen magnetic resonance spectroscopy
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone	No Treatment
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device	(no study treatment - observation only)
Measure Participants	9	9
Mean (Standard Deviation) [Percent (Hepatic fat fraction, percent)]	-3.0 (5.2)	0.3 (3.5)

2. Secondary Outcome

Title	Change in Aspartate Aminotransferase (AST)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone	No Treatment
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device	(no study treatment - observation only)
Measure Participants	10	10
Mean (Standard Deviation) [units per liter]	-3 (9)	-1 (4)

3. Secondary Outcome

Title	Change in Alanine Aminotransferase (ALT)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone	No Treatment
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device	(no study treatment - observation only)
Measure Participants	10	10
Mean (Standard Deviation) [units per liter]	-2 (9)	1 (8)

4. Secondary Outcome

Title	Change in Gamma Glutamyl Transferase
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone	No Treatment
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device	(no study treatment - observation only)
Measure Participants	10	10
Mean (Standard Deviation) [units per liter]	-9 (30)	5 (9)

5. Secondary Outcome

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
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone	No Treatment
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device	(no study treatment - observation only)
Measure Participants	9	9
Mean (Standard Deviation) [square centimeters]	-6 (50)	6 (24)

Adverse Events

Time Frame	Adverse events were collected from participants while they were enrolled in the 6 month study period.
Adverse Event Reporting Description	Participants were asked about adverse events at every study visit. Of note, participants receiving GH were seen for 4 additional visits compared to those receiving no treatment in this open-label study, and thus had more visits at which adverse events were assessed.
Arm/Group Title	Growth Hormone		No Treatment
Arm/Group 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. somatropin: Norditropin (growth hormone) given by injection using a pen-device		(no study treatment - observation only)
All Cause Mortality
	Growth Hormone		No Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/11 (0%)
Serious Adverse Events
	Growth Hormone		No Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		0/11 (0%)
Surgical and medical procedures
Hospitalization	1/13 (7.7%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Growth Hormone		No Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/13 (69.2%)		1/11 (9.1%)
Gastrointestinal disorders
Gingival hyperplasia	1/13 (7.7%)	1	0/11 (0%)	0
General disorders
Injection Site Bruising	4/13 (30.8%)	6	0/11 (0%)	0
Immune system disorders
Acute allergic reaction	1/13 (7.7%)	1	0/11 (0%)	0
Infections and infestations
Upper Respiratory Tract Infection	2/13 (15.4%)	2	0/11 (0%)	0
Injury, poisoning and procedural complications
Motor Vehicle Accident	1/13 (7.7%)	1	0/11 (0%)	0
Musculoskeletal and connective tissue disorders
Tightness in Jaw	1/13 (7.7%)	1	0/11 (0%)	0
Nervous system disorders
Headache transient	4/13 (30.8%)	5	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Acne	1/13 (7.7%)	1	0/11 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.