Trial Outcomes & Findings for Study of Losartan in the Treatment of NAFLD in Children (NCT NCT01913470)

NCT ID: NCT01913470

Last Updated: 2017-05-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Baseline (Weeks 0 and 14), Endpoint (Weeks 8 and 22)

Results posted on

2017-05-15

Participant Flow

Children were recruited from the patient population of Children's Healthcare of Atlanta and the Emory Children's Center Clinics.

Of the 16 individuals who signed the consent form, 4 were found to be ineligible to participate during screening process, resulting in 12 participants who began the study treatment.

Participant milestones

Participant milestones
Measure	Losartan Followed by Placebo Recipients of treatment with losartan for 8 weeks followed by 8 weeks of treatment with a placebo	Placebo Followed by Losartan Recipients of treatment with a placebo for 8 weeks followed by 8 weeks of treatment with losartan.
Overall Study STARTED	5	7
Overall Study COMPLETED	5	4
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Losartan Followed by Placebo Recipients of treatment with losartan for 8 weeks followed by 8 weeks of treatment with a placebo	Placebo Followed by Losartan Recipients of treatment with a placebo for 8 weeks followed by 8 weeks of treatment with losartan.
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Study of Losartan in the Treatment of NAFLD in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Losartan Followed by Placebo n=5 Participants Recipients of treatment with losartan for 8 weeks followed by 8 weeks of treatment with a placebo.	Placebo Followed by Losartan n=7 Participants Recipients of treatment with a placebo for 8 weeks followed by 8 weeks of treatment with losartan.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Weeks 0 and 14), Endpoint (Weeks 8 and 22)

Population: In this blinded, crossover treatment, study participants received losartan or a placebo for 8 weeks, then completed a 6 week washout period before crossing over to the other treatment for 8 weeks. The placebo results for four participants in the losartan followed by placebo arm were not usable due to carry over effects from the active treatment.

Outcome measures

Outcome measures
Measure	Losartan n=9 Participants Recipients of treatment with losartan for 8 weeks.	Placebo n=5 Participants Recipients of treatment with a placebo for 8 weeks.
Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment) ALT at Baseline (weeks 0 and 14)	136.44 U/L Standard Deviation 80.06	117.40 U/L Standard Deviation 56.42
Change in Alanine Aminotransferase (ALT) From Baseline to End of Treatment (8 Weeks of Treatment) ALT at End of Treatment (weeks 8 and 22)	112.78 U/L Standard Deviation 69.64	89.40 U/L Standard Deviation 35.26

SECONDARY outcome

Timeframe: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)

Population: The placebo results for four participants in the losartan followed by placebo arm were not usable due to carry over effects from the active treatment. One additional participant in each treatment group is missing the end of treatment cholesterol level measurement.

For children, a cholesterol level of less than 170 is considered acceptable, 170-199 is borderline high, and 200 and over is high.

Outcome measures

Outcome measures
Measure	Losartan n=9 Participants Recipients of treatment with losartan for 8 weeks.	Placebo n=5 Participants Recipients of treatment with a placebo for 8 weeks.
Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment) Cholesterol at baseline (week 0 or 14)	137.67 mg/dL Standard Deviation 28.81	152.80 mg/dL Standard Deviation 18.79
Change in Cholesterol Levels From Baseline to End of Treatment (8 Weeks of Treatment) Cholesterol at end of treatment (week 8 and/or 22)	132.38 mg/dL Standard Deviation 23.84	144.00 mg/dL Standard Deviation 13.47

SECONDARY outcome

Timeframe: Baseline (Week 0 and 14), End of treatment (Week 8 and 22)

Population: The placebo results for four participants in the losartan followed by placebo arm were not usable due to carry over effects from the active treatment. One participant is missing data for the endpoint measurement of triglyceride levels, following 8 weeks of losartan 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.

Outcome measures

Outcome measures
Measure	Losartan n=9 Participants Recipients of treatment with losartan for 8 weeks.	Placebo n=5 Participants Recipients of treatment with a placebo for 8 weeks.
Change in Triglyceride Levels From Baseline to End of Treatment (8 Weeks of Treatment) Triglyceride at baseline (week 0 or 14)	97.11 mg/dL Standard Deviation 50.27	69.60 mg/dL Standard Deviation 11.87
Change in Triglyceride Levels From Baseline to End of Treatment (8 Weeks of Treatment) Triglyceride at end of treatment (week 8 or 22)	65.75 mg/dL Standard Deviation 25.34	80.40 mg/dL Standard Deviation 16.59

SECONDARY outcome

Timeframe: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)

Population: The placebo results for four participants in the losartan followed by placebo arm were not usable due to carry over effects from the active treatment. One participant is missing the endpoint measurement for free fatty acid levels, following the 8 week losartan treatment phase.

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.

Outcome measures

Outcome measures
Measure	Losartan n=9 Participants Recipients of treatment with losartan for 8 weeks.	Placebo n=5 Participants Recipients of treatment with a placebo for 8 weeks.
Change in Fatty Acid Levels From Baseline to End of Treatment (8 Weeks of Treatment) Fatty acid at Baseline (week 0 and 14)	0.38 mEq/L Standard Deviation 0.17	0.41 mEq/L Standard Deviation 0.12
Change in Fatty Acid Levels From Baseline to End of Treatment (8 Weeks of Treatment) Fatty acid at end of treatment (week 8 and 22)	0.45 mEq/L Standard Deviation 0.11	0.38 mEq/L Standard Deviation 0.12

SECONDARY outcome

Timeframe: Baseline (Week 0 and 14), End of Treatment (Week 8 and 22)

Population: The placebo results for four participants in the losartan followed by placebo arm were not usable due to carry over effects from the active treatment. An additional participant is missing HOMA-IR data from the placebo phase of the study.

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.

Outcome measures

Outcome measures
Measure	Losartan n=9 Participants Recipients of treatment with losartan for 8 weeks.	Placebo n=4 Participants Recipients of treatment with a placebo for 8 weeks.
Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) Between Baseline and End of Treatment (8 Weeks of Treatment) HOMA-IR at Baseline (week 0 or 14)	20.12 units on a scale Standard Deviation 11.31	6.59 units on a scale Standard Deviation 2.91
Changes in Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR) Between Baseline and End of Treatment (8 Weeks of Treatment) HOMA-IR at end of treatment (week 8 or 22)	9.35 units on a scale Standard Deviation 4.81	11.67 units on a scale Standard Deviation 4.42

SECONDARY outcome

Timeframe: Baseline, Week 8, Week 14, Week 22

Population: The placebo results for four participants in the losartan followed by placebo arm were not usable due to carry over effects from the active treatment. One additional participant is missing PAI-1 data from the placebo phase of the study.

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

Outcome measures

Outcome measures
Measure	Losartan n=9 Participants Recipients of treatment with losartan for 8 weeks.	Placebo n=4 Participants Recipients of treatment with a placebo for 8 weeks.
Changes in Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations Between Baseline and End of Treatment PAI-1 at Baseline (week 0 or 14)	5.25 ng/mL Standard Deviation 1.55	6.39 ng/mL Standard Deviation 2.57
Changes in Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations Between Baseline and End of Treatment PAI-1 at end of treatment (week 8 or 22)	5.04 ng/mL Standard Deviation 2.50	6.58 ng/mL Standard Deviation 4.01

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 8, Week 14, and Week 22

The normal range for AST in children is 0 - 60 IU/L. AST can respond rapidly to treatment so decreases between Baseline and subsequent measurements indicate positive effects of treatment.

Outcome measures

Outcome measures
Measure	Losartan n=9 Participants Recipients of treatment with losartan for 8 weeks.	Placebo n=5 Participants Recipients of treatment with a placebo for 8 weeks.
Change in Aspartate Aminotransferase (AST) From Baseline to End of Treatment AST at Baseline (week 0 or 14)	66.89 IU/L Standard Deviation 28.01	51.60 IU/L Standard Deviation 18.05
Change in Aspartate Aminotransferase (AST) From Baseline to End of Treatment AST from Baseline to Week 22	54.22 IU/L Standard Deviation 21.52	37.80 IU/L Standard Deviation 10.71

Adverse Events

Losartan

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Losartan n=9 participants at risk Recipients of treatment with losartan for 8 weeks.	Placebo n=5 participants at risk Recipients of treatment with a placebo for 8 weeks.
Ear and labyrinth disorders Ear ache	11.1% 1/9 • Number of events 1 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	0.00% 0/5 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
Eye disorders Blurred vision	22.2% 2/9 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	0.00% 0/5 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
General disorders Abdominal Pain	11.1% 1/9 • Number of events 1 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	40.0% 2/5 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
General disorders Chest Pain	22.2% 2/9 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	0.00% 0/5 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
General disorders Dizziness	33.3% 3/9 • Number of events 4 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	40.0% 2/5 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
General disorders Fatigue	11.1% 1/9 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	0.00% 0/5 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
General disorders Lack of Concentration	22.2% 2/9 • Number of events 3 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	0.00% 0/5 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
General disorders Nausea	22.2% 2/9 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	40.0% 2/5 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
Musculoskeletal and connective tissue disorders Muscle Pain	33.3% 3/9 • Number of events 3 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	20.0% 1/5 • Number of events 1 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 1/9 • Number of events 3 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	40.0% 2/5 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	55.6% 5/9 • Number of events 7 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	40.0% 2/5 • Number of events 3 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
Respiratory, thoracic and mediastinal disorders Sinus Infection	0.00% 0/9 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	40.0% 2/5 • Number of events 2 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	11.1% 1/9 • Number of events 1 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	20.0% 1/5 • Number of events 1 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.
Skin and subcutaneous tissue disorders Hives	0.00% 0/9 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.	20.0% 1/5 • Number of events 1 • Adverse event details were collected throughout the duration of study participation, from the Baseline visit through the Week 28 follow up visit. For this study, an adverse event is considered any untoward medical occurrence in a subject participating in a clinical study that does not necessarily have a causal relationship with the study drug. It can also mean any unfavorable and unintended sign (including laboratory findings, symptom, or disease) temporarily associated with the use of losartan or placebo, whether or not directly related to losartan or not.

Additional Information

Miriam Vos, MD, MSPH

Emory University

Phone: 404-727-9930

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place