Clinical trial NCT01167088: A Study to Compare MitoQ and Placebo to Treat Non-alcoholic Fatty Liver Disease (NAFLD)
Official title: A Double-blind Randomised Placebo-controlled Multicentre Study of 40mg MitoQ and Placebo for the Treatment of Participants With Raised Liver Enzymes Due to Non-Alcoholic Fatty Liver Disease (NAFLD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: Double-blind
Placebo-controlled
Non-alcoholic fatty liver disease
NAFLD
Lead sponsor: Antipodean Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-07-22
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate whether a new medicine, called mitoquinone, will reduce raised liver enzymes due to NAFLD and to see if it is safe.


Eligibility criteria: Inclusion Criteria:

1. Provide written informed consent
2. NAFLD as determined by raised ALT (\> 1.5 x ULN corresponding to \>29U/L for females and \>45U/L for males\] in the screening period and on at least two other occasions in the previous 6 months) and ultrasound evidence of steatosis (in the previous 12 months).
3. Be aged between 18 - 70 years on the day of consent
4. Expect to not require or make any changes in all their current concomitant medications (prescribed and over-the-counter) for the duration of their participation in the study
5. Female patients with reproductive potential must have a negative serum pregnancy test within 14 days prior to start of trial and must agree to use a medically acceptable method of contraception throughout the treatment period and for 1 month after discontinuation of treatment. Acceptable methods of contraception include IUD, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive pessary)

Exclusion Criteria:

1. Alcohol consumption \> 14 units/week for females and 21 units/week for males
2. Hepatocellular carcinoma (HCC) or suspicion of HCC
3. Presence of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV)
4. Renal impairment (creatinine \> 1.5 x ULN) or hepatorenal syndrome
5. Chronic pancreatitis
6. Hospitalization for liver disease within 60 days of the baseline visit
7. Previously diagnosed diabetes / treatment with insulin sensitizing agents
8. Severe or morbid obesity (BMI\>40kg/m2)
9. ALT or AST \> 10 times ULN
10. Liver transplant recipients
11. Corticosteroids in the past 30 days
12. Any participant who has received any investigational drug or device within 30 days of dosing, or who is scheduled to receive another investigational drug or device during the course of this trial
13. A history of a malignancy other than treated basal cell or squamous cell carcinoma of the skin; those with a history of malignancy that has been treated with no recurrence within the last 2 years are not excluded
14. Females who are pregnant or breastfeeding
15. Use of Coenzyme Q10, either prescribed or purchased over-the-counter, are prohibited during the study, except for doses of up to 25mg/day which have been stable for 30 days prior to baseline. Higher doses require a 7 day washout prior to baseline.
16. Use of Vitamin E, either prescribed or purchased over-the-counter, are prohibited during the study, except for doses of up to 200IU/day which have been stable for 30 days prior to baseline. Higher doses require a 90 day washout prior to baseline.
17. Any changes to prescription medication in the 30 days prior to baseline
18. A history of a hypersensitivity reaction to any components of the study drug or structurally similar compounds including Coenzyme Q10 and idebenone
19. Unable to swallow tablets whole
20. Patients with histological or clinical evidence of established cirrhosis
21. Suffering from any other disease or condition which, in the opinion of the investigator, means that it would not be in the patient's best interest to participate in this study

Primary outcomes:
measure: Percentage change in ALT (relative to baseline) at the end of the treatment period (Day 90) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Absolute change in ALT level (relative to baseline) at end of treatment period for MitoQ compared with placebo
timeFrame: Baseline and 3 months
measure: The percentage of participants whose ALT levels are in the normal range at the end of the treatment period.
timeFrame: 3 months
measure: The difference in the percentage and absolute rates of change in ALT levels between MitoQ and placebo.
timeFrame: Baseline to 3 months
measure: The percentage and absolute change in AST at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: The change in HOMA-IR at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: The change in HbA1c at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: The percentage and absolute change in GGT and alkaline phosphatase at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: Areas under the ALT, AST, GGT and alkaline phosphatase curves from baseline to the end of the treatment period.
timeFrame: Baseline to 3 months
measure: The change in markers of liver inflammation (leptin and adiponectin) at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: The change in biomarkers of mitochondrial function and oxidative damage (isoprostanes) at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: The change in blood pressure at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: The change in blood lipid profile at the end of the treatment period (relative to baseline) for MitoQ compared with placebo.
timeFrame: Baseline and 3 months
measure: Incidence of adverse events
timeFrame: Baseline to Follow-up (total 4 months)
measure: Clinically relevant deterioration in laboratory variables
timeFrame: Baseline to Follow-up (total 4 months)
measure: Clinically relevant deterioration in vital signs
timeFrame: Baseline to Follow-up (total 4 months)
measure: Clinically relevant deterioration in ECG parameters
timeFrame: Baseline to Follow-up (total 4 months)
Other outcomes:
Locations:
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Newcastle University Medical School, UK
name: Chris Day, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: