Hepatic SteatosisPhase 2/3APPLENCT02157974

Liver and Fat Regulation in Overweight Adolescent Girls

A Phase 2/3 study testing Byetta 5Mcg Pen Injection in people with Hepatic Steatosis and Polycystic Ovarian Syndrome, run by University of Colorado, Denver at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 12 to 21 years, women onlyHealthy volunteers can take part
Conditions the study is for: Hepatic Steatosis, Polycystic Ovarian Syndrome, Obesity
What is being tested?: Byetta 5Mcg Pen Injection
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 92 participants
Where: 1 siteUnited States
Study dates: Aug 2014to Dec 2022
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 21 years
Women only
Healthy volunteers accepted
Child, Adult

Who may be able to join

Females
2 years post-menarche
BMI percentile >90%

Who cannot join

Type 2 diabetes
Anemia
Liver disease
Medications known to effect insulin sensitivity
Cause of oligomenorrhea or hirsutism other than PCOS,
>3 hours a week of moderate exercise.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Colorado Anshutz Medical Campus/Children's Hospital Colorado
Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls

Women with polycystic ovarian syndrome (PCOS) have increased rates of hepatic steatosis compared to weight similar women with regular menses. It is unclear if this is related to high testosterone or insulin resistance. The investigators will assess hepatic glucose release, rates of lipolysis and hepatic de novo lipogenesis in the fasted and postprandial state to determine if alterations in the processes contribute to hepatic steatosis. Participants will be overweight, sedentary girls with or without PCOS. Those with PCOS will either be medication naive, or must be taking metformin or combined oral contraceptives (COCPs) for a period of at least 6 months prior to study procedures.

Read the detailed description

Hepatic glucose release will be assessed with a stable isotope glycerol tracer, lipolysis with a glycerol tracer, and hepatic de novo lipogenesis with an acetate tracer. Data will be collected fasting and after a glucose challenge. The degree of hepatic steatosis and abdominal fat partitioning will be assessed with Magnetic Resonance Imaging (MRI), and total body composition with Dual-energy X-ray absorptiometry (DEXA).

Conditions: Hepatic Steatosis, Polycystic Ovarian Syndrome, Obesity
Being tested: Byetta 5Mcg Pen Injection
Medical subject headings: Fatty Liver, Polycystic Ovary Syndrome, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Byetta 5Mcg Pen InjectionDrug
Also called Exenatide
10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola

Study groups in NCT02157974
Study group	Role	What they receive
PCOS, medication naive + Byetta	Experimental	PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Receives: Drug: Byetta 5Mcg Pen Injection
Control	No intervention	Up to 25 girls without PCOS
PCOS medication naive	No intervention	Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.
PCOS on COCPs	No intervention	Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.
PCOS on metformin	No intervention	Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures

What is being measured

The primary outcome is the main question the study is designed to answer.

Hepatic Glucose Release
Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. Glucose rate of appearance reflects the amount of glucose being release by primarily the liver during fasting. A higher glucose rate of appearance is often seen with dysglycemia
Measured: Measured up to 4 months from enrollment

Secondary outcomes (4)

Hepatic Phosphate Concentrations
Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy. The ratio of the following will be reported over total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG)
Measured: Measured up to 4 months from enrollment
Rates of Lipolysis
Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer. Glycerol rate of appearance reflects the amount of glycerol being released into the blood stream as a results of lipolysis. Higher rates of lipolysis are thought to be associated with insulin resistance.
Measured: Measured up to 4 months from enrollment
Hepatic Fat Fraction
Amount of fat in the liver measured by MRI and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver.
Measured: Measured up to 4 months from enrollment
Hepatic de Novo Lipogenesis
Hepatic de novo lipogenesis will be measured by with an acetate tracer by mass spectroscopy. De novo lipogenesis can contribute to non-alcoholic fatty liver disease, so having a lower value is better.
Measured: Measured up to 4 months from enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2014Dec 2022

First posted6 Jun 2014 (estimated)
Study startAug 2014
Primary completionDec 2022
Study completionDec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Hepatic SteatosisStudies of the same condition, open and under way.
More trials run by University of Colorado, DenverThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 92 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02157974
Sponsor's protocol ID: 14-0542
Other IDs: UL1TR001082, K23DK107871
Acronym: APPLE
Status last verified: May 2024
First submitted: 4 Jun 2014
Last updated: 4 Jun 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Data will only be shared with IRB approved personnel.

Publications

Boster JM, Cree MG, Kelsey MM, Nadeau KJ, Chaidez A, Pan Z, Sundaram SS. Relative Skeletal Muscle Mass Is Associated With Hepatic Steatosis in Adolescents With Overweight and Obesity. Pediatr Obes. 2026 Apr;21(4):e70108. doi: 10.1111/ijpo.70108.
PubMed 42014131
Carreau AM, Pyle L, Garcia-Reyes Y, Rahat H, Vigers T, Jensen T, Scherzinger A, Nadeau KJ, Cree-Green M. Clinical prediction score of nonalcoholic fatty liver disease in adolescent girls with polycystic ovary syndrome (PCOS-HS index). Clin Endocrinol (Oxf). 2019 Oct;91(4):544-552. doi: 10.1111/cen.14062. Epub 2019 Aug 16.
PubMed 31301251
Simon SL, McWhirter L, Diniz Behn C, Bubar KM, Kaar JL, Pyle L, Rahat H, Garcia-Reyes Y, Carreau AM, Wright KP, Nadeau KJ, Cree-Green M. Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3525-3534. doi: 10.1210/jc.2018-02385.
PubMed 30888398

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Recruiting
Dietary Intervention Study on Liver Health in Young Adults
Liver Health
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
Not yet recruiting
Personalized Dietary Feedback to Reduce Hepatic Steatosis in Patients With MASLD
MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease), MetALD

All Hepatic Steatosis trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessment of Hepatic Glucose and Fat Regulation in Overweight Adolescent Girls
ClinicalTrials.gov ID: NCT02157974
Acronym / sponsor ID: APPLE / 14-0542
Conditions: Hepatic Steatosis, Polycystic Ovarian Syndrome, Obesity
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 92 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Collaborators: National Center for Advancing Translational Sciences (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study start: Aug 2014 (actual)
Primary completion: Dec 2022 (actual)
Study completion: Dec 2022 (actual)
First posted: 6 Jun 2014 (estimated)
Results: Posted 4 Jun 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
PCOS, medication naive + Byetta	Experimental	Drug: Byetta 5Mcg Pen InjectionPCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta.
Control	No intervention	–Up to 25 girls without PCOS
PCOS medication naive	No intervention	–Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months.
PCOS on COCPs	No intervention	–Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures.
PCOS on metformin	No intervention	–Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures

Who may qualify

Ages: 12 to 21 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (3 listed)

Females
2 years post-menarche
BMI percentile >90%

Key exclusion criteria (6 listed)

Type 2 diabetes
Anemia
Liver disease
Medications known to effect insulin sensitivity
Cause of oligomenorrhea or hirsutism other than PCOS,

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Byetta 5Mcg Pen InjectionAlso: Exenatide10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola	Drug	PCOS, medication naive + Byetta

Primary outcome

Hepatic Glucose Release
Time frame: Measured up to 4 months from enrollment
Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. Glucose rate of appearance reflects the amount of glucose being release by primarily the liver during fasting. A higher glucose rate of appearance is often seen with dysglycemia

4 secondary outcomes

Hepatic Phosphate Concentrations
Time frame: Measured up to 4 months from enrollment
Rates of Lipolysis
Time frame: Measured up to 4 months from enrollment
Hepatic Fat Fraction
Time frame: Measured up to 4 months from enrollment
Hepatic de Novo Lipogenesis
Time frame: Measured up to 4 months from enrollment

Results and safety

Results posted to the registry on 4 Jun 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control	24	24
PCOS Medication Naive	42	39
PCOS, Medication Naive + Byetta	10	10
PCOS on COCPs	10	10
PCOS on Metformin	6	6

Primary outcome: Hepatic Glucose Release

Time frame: Measured up to 4 months from enrollment. Mean (Standard Deviation). Unit: mg/kg/min

Measure	Control n = 16	PCOS Medication Naive n = 30	PCOS, Medication Naive + Byetta n = 9	PCOS on COCPs n = 8	PCOS on Metformin n = 4
Value	1.85 (1.24)	1.46 (0.21)	1.54 (0.38)	1.88 (0.49)	1.57 (0.07)

Population analysed: Not all participants had complete data to analyze the glucose RA.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Measured up to 4 months from enrollment. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control	0 of 24 (0%)	0 of 24 (0%)	0 of 24
PCOS Medication Naive	0 of 42 (0%)	0 of 42 (0%)	0 of 42
PCOS, Medication Naive + Byetta	0 of 10 (0%)	0 of 10 (0%)	0 of 10
PCOS on COCPs	0 of 10 (0%)	0 of 10 (0%)	0 of 10
PCOS on Metformin	0 of 6 (0%)	0 of 6 (0%)	0 of 6

Limitations and caveats (from the sponsor): Due to the Covid-19 outbreak, we were unable to enroll the last 4 participants in the PCOS on metformin arm, so the results may not reach statistical significance. We had delays in getting tracer results due to the mass spec machine being down, and once raw data was obtained, we needed to work with a mathematician to calculate the rates of appearance of the tracer results.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42014131Boster JM, Cree MG, Kelsey MM, Nadeau KJ, Chaidez A, Pan Z, Sundaram SS. Relative Skeletal Muscle Mass Is Associated With Hepatic Steatosis in Adolescents With Overweight and Obesity. Pediatr Obes. 2026 Apr;21(4):e70108. doi: 10.1111/ijpo.70108.
Derived from this study: PubMed 31301251Carreau AM, Pyle L, Garcia-Reyes Y, Rahat H, Vigers T, Jensen T, Scherzinger A, Nadeau KJ, Cree-Green M. Clinical prediction score of nonalcoholic fatty liver disease in adolescent girls with polycystic ovary syndrome (PCOS-HS index). Clin Endocrinol (Oxf). 2019 Oct;91(4):544-552. doi: 10.1111/cen.14062. Epub 2019 Aug 16.
Derived from this study: PubMed 30888398Simon SL, McWhirter L, Diniz Behn C, Bubar KM, Kaar JL, Pyle L, Rahat H, Garcia-Reyes Y, Carreau AM, Wright KP, Nadeau KJ, Cree-Green M. Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3525-3534. doi: 10.1210/jc.2018-02385.
Individual participant dataSharing planned: No. Data will only be shared with IRB approved personnel.

Related trials for Hepatic Steatosis

Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Recruiting
Dietary Intervention Study on Liver Health in Young Adults
Liver Health
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
Not yet recruiting
Personalized Dietary Feedback to Reduce Hepatic Steatosis in Patients With MASLD
MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease), MetALD

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Melanie Cree Green, MD, PhD principal investigator

Department of Endocrinology

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Byetta 5Mcg Pen Injection in people with Hepatic Steatosis and Polycystic Ovarian Syndrome, run by University of Colorado, Denver at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hepatic Glucose Release (time frame: Measured up to 4 months from enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02157974, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2024.