NAFLDPhase 2NCT01913470
Study of Losartan in the Treatment of NAFLD in Children
A Phase 2 study testing Losartan in people with NAFLD, run by Miriam Vos, MD at 1 site in United States.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease among children and is closely associated with obesity and the metabolic syndrome. NAFLD increases risk of mortality and natural history studies of adults show that NAFLD is an independent risk factor for cardiovascular disease. Read more about this study
- Who is it for?
- Ages 11 to 19 years
- Conditions the study is for
- NAFLD
- What is being tested?
- Losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Dec 2015
- Phase
- Phase 2
- 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 11 to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Body Mass Index (BMI) > 85th% for age and gender
- History of definite or borderline nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy using NASH Clinical Research Network (CRN) criteria
- At least 2 months of attempted lifestyle changes after liver biopsy
- Current ALT ≥ 3 times normal (69 U/L for girls, 78 U/L for boys) at enrollment
- Glomerular filtration rate (GRF) > 90
- Weight ≥ 62.5 kg
Who cannot join
- Other chronic illness requiring daily medication (except medications for mild mental illness, acid reflux, allergies, stable attention deficit hyperactivity disorder (ADHD), or asthma)
- Supplement or anti-oxidant therapy within past 2 weeks
- Renal insufficiency
- Cirrhosis and liver synthetic dysfunction (International Normalized Ratio ≥ 1.5)
- History of hypotension
- Diabetes (or fasting glucose > 125 mg/dL)
- Acute illness within past 2 weeks prior to enrollment (fever > 100.4ºF)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University / Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
About this study
Official title: A Pilot Study of Losartan in the Treatment of Pediatric NAFLD
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease among children and is closely associated with obesity and the metabolic syndrome. NAFLD increases risk of mortality and natural history studies of adults show that NAFLD is an independent risk factor for cardiovascular disease. Pediatric NAFLD is particularly concerning from a public health standpoint, as it represents an early and possibly more aggressive form of the disease. Currently there is no effective treatment for pediatric NAFLD.
Losartan is an orally-administered angiotensin II receptor antagonist which is currently on the market to treat high blood pressure. The renin-angiotensin-aldosterone (RAA) system has been shown to be important in many disease states including renal disease, cardiovascular disease, and NAFLD. Angiotensin antagonists are a class of medications that has been proposed as a novel treatment of NAFLD in part because they would treat both the factors increasing cardiovascular (CVD) risks as well as potentially improve steatosis, fibrosis and hepatic inflammation.
This study is a randomized, double-blinded, placebo-controlled pilot study to evaluate whether 8 weeks of Losartan will decrease inflammatory markers among children ages 12-19 with a current diagnosis of NAFLD. Efficacy will be assessed by improvement in alanine aminotransferase (ALT) from baseline. Secondary endpoints will include aspartate aminotransferase (AST), cytokeratin 18 levels, and fasting triglyceride levels among others. Safety will be assessed by the recording of adverse events, clinical laboratory parameters, vital signs and physical examinations.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar, Losartan Potassium Tablets, Serial Number: 74193404
Oral tablet to be taken once daily at 0.4mg/kg/day (max 25mg) for one week and then increased to 0.8mg/kg/day (max 50mg) for 7 additional weeks.
| Study group | Role | What they receive |
|---|---|---|
| Losartan then Placebo | Experimental | 0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks then placebo pill for 8 weeks Receives: Drug: Losartan |
| Sugar pill | Experimental | placebo pill taken for 8 weeks then 0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks Receives: Drug: Losartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment)
The principal objective of this blinded, placebo controlled, crossover pilot study is to evaluate whether 8 weeks of losartan in children with nonalcoholic steatohepatitis (NASH) will decrease inflammation as measured by ALT.
Measured: Baseline (Weeks 0 and 14), Endpoint (Weeks 8 and 22)
Secondary outcomes (5)
Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment)
For children, a cholesterol level of less than 170 is considered acceptable, 170-199 is borderline high, and 200 and over is high.
Measured: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)
Change in Triglyceride Levels From Baseline to End of Treatment (8 Weeks of Treatment)
For children aged 10 to 19, triglyceride levels of less than 90 is considered acceptable, 90 to 129 is borderline high, and greater than or equal to 130 and over is high.
Measured: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)
Change in Fatty Acid Levels From Baseline to End of Treatment (8 Weeks of Treatment)
In human studies, losartan has been shown to decrease serum free fatty acids, thus any decrease in this measurement indicates a positive response to losartan.
Measured: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)
Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) Between Baseline and End of Treatment (8 Weeks of Treatment)
Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) is an equation which indicates the degree of insulin resistance, where higher scores equate to greater insulin resistance. HOMA-IR is calculated as fasting glucose (mg/dl) × insulin (mU/L)/405. A HOMA-IR value >2.0 in prepubertal children and >2.6 in pubertal children, may be considered a warning sign for pediatricians to further investigate insulin resistance.
Measured: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)
Changes in Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations Between Baseline and End of Treatment
PAI-1 is an acute-phase protein that is associated with both injury and inflammation, and has been found to be elevated in adolescents with significant hepatic steatosis. The reference range for PAI-1 in fasting adults is 3-72 ng/mL
Measured: Baseline, Week 8, Week 14, Week 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2013 (estimated)
- Study startJul 2013
- Primary completionDec 2015
- Study completionDec 2015
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 (1)Papers the sponsor has linked to this study.
- Other trials for NAFLDStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Miriam Vos, MD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Children's Healthcare of Atlanta
- Responsible party
- Sponsor-investigator, Miriam Vos, MD, Emory University
- Investigators
- Miriam Vos, MD, MSPH, Principal investigator, Emory University / Children's Healthcare of Atlanta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01913470
- Sponsor's protocol ID
- IRB00062895
- Other IDs
- 1R03DK096157-01A1, 1R03DK096157-01
- Status last verified
- Apr 2017
- First submitted
- 8 Jul 2013
- Last updated
- 15 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Vos MB, Jin R, Konomi JV, Cleeton R, Cruz J, Karpen S, Rodriguez DS, Frediani JK, McCracken C, Welsh J. A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease. Pilot Feasibility Stud. 2018 Jun 5;4:109. doi: 10.1186/s40814-018-0306-4. eCollection 2018.
PubMed 29992039
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Losartan in the Treatment of Pediatric NAFLD
- ClinicalTrials.gov ID
- NCT01913470
- Acronym / sponsor ID
- IRB00062895
- Conditions
- NAFLD
- Keywords
- NAFLD, Non-alcoholic Fatty Liver Disease, Obesity, Pediatrics, Children, Losartan, Cozaar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Miriam Vos, MDUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Children's Healthcare of Atlanta
- Study start
- Jul 2013
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 1 Aug 2013 (estimated)
- Results
- Posted 15 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease among children and is closely associated with obesity and the metabolic syndrome. NAFLD increases risk of mortality and natural history studies of adults show that NAFLD is an independent risk factor for cardiovascular disease. Pediatric NAFLD is particularly concerning from a public health standpoint, as it represents an early and possibly more aggressive form of the disease. Currently there is no effective treatment for pediatric NAFLD.
Losartan is an orally-administered angiotensin II receptor antagonist which is currently on the market to treat high blood pressure. The renin-angiotensin-aldosterone (RAA) system has been shown to be important in many disease states including renal disease, cardiovascular disease, and NAFLD. Angiotensin antagonists are a class of medications that has been proposed as a novel treatment of NAFLD in part because they would treat both the factors increasing cardiovascular (CVD) risks as well as potentially improve steatosis, fibrosis and hepatic inflammation.
This study is a randomized, double-blinded, placebo-controlled pilot study to evaluate whether 8 weeks of Losartan will decrease inflammatory markers among children ages 12-19 with a current diagnosis of NAFLD. Efficacy will be assessed by improvement in alanine aminotransferase (ALT) from baseline. Secondary endpoints will include aspartate aminotransferase (AST), cytokeratin 18 levels, and fasting triglyceride levels among others. Safety will be assessed by the recording of adverse events, clinical laboratory parameters, vital signs and physical examinations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Losartan then Placebo | Experimental | Drug: Losartan0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks then placebo pill for 8 weeks |
| Sugar pill | Experimental | Drug: Losartanplacebo pill taken for 8 weeks then 0.4mg/kg/day (max 25mg) for one week and then increase to 0.8mg/kg/day (max 50mg) for 7 additional weeks |
Who may qualify
- Ages
- 11 to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Body Mass Index (BMI) > 85th% for age and gender
- History of definite or borderline nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy using NASH Clinical Research Network (CRN) criteria
- At least 2 months of attempted lifestyle changes after liver biopsy
- Current ALT ≥ 3 times normal (69 U/L for girls, 78 U/L for boys) at enrollment
- Glomerular filtration rate (GRF) > 90
Key exclusion criteria (8 listed)
- Other chronic illness requiring daily medication (except medications for mild mental illness, acid reflux, allergies, stable attention deficit hyperactivity disorder (ADHD), or asthma)
- Supplement or anti-oxidant therapy within past 2 weeks
- Renal insufficiency
- Cirrhosis and liver synthetic dysfunction (International Normalized Ratio ≥ 1.5)
- History of hypotension
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 |
|---|---|---|
| LosartanAlso: Cozaar, Losartan Potassium Tablets, Serial Number: 74193404Oral tablet to be taken once daily at 0.4mg/kg/day (max 25mg) for one week and then increased to 0.8mg/kg/day (max 50mg) for 7 additional weeks. | Drug | Losartan then Placebo, Sugar pill |
Primary outcome
Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment)
Time frame: Baseline (Weeks 0 and 14), Endpoint (Weeks 8 and 22)
The principal objective of this blinded, placebo controlled, crossover pilot study is to evaluate whether 8 weeks of losartan in children with nonalcoholic steatohepatitis (NASH) will decrease inflammation as measured by ALT.
5 secondary outcomes
Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment)
Time frame: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)
Change in Triglyceride Levels From Baseline to End of Treatment (8 Weeks of Treatment)
Time frame: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)
Change in Fatty Acid Levels From Baseline to End of Treatment (8 Weeks of Treatment)
Time frame: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)
Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) Between Baseline and End of Treatment (8 Weeks of Treatment)
Time frame: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)
Changes in Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations Between Baseline and End of Treatment
Time frame: Baseline, Week 8, Week 14, Week 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29992039Vos MB, Jin R, Konomi JV, Cleeton R, Cruz J, Karpen S, Rodriguez DS, Frediani JK, McCracken C, Welsh J. A randomized, controlled, crossover pilot study of losartan for pediatric nonalcoholic fatty liver disease. Pilot Feasibility Stud. 2018 Jun 5;4:109. doi: 10.1186/s40814-018-0306-4. eCollection 2018.
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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.
Miriam Vos, MD, MSPH principal investigator
Emory University / Children's Healthcare of Atlanta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Losartan in people with NAFLD, run by Miriam Vos, MD 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 6 inclusion and 8 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 15 May 2017. 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 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.
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 15 May 2017). 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?
Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment) (time frame: Baseline (Weeks 0 and 14), Endpoint (Weeks 8 and 22)). 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 NCT01913470, which also lists 1 linked publication.
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 15 May 2017; AzTrials last refreshed its copy on 8 Nov 2026.