The Effect of Acetaminophen on Non-alcoholic Fatty Liver Disease Patients
| Status: | Recruiting |
|---|---|
| Conditions: | Gastrointestinal, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 4/2/2016 |
| Start Date: | June 2014 |
| End Date: | June 2017 |
| Contact: | Mazen Noureddin |
| Email: | noureddi@usc.edu |
| Phone: | 323-442-8500 |
The Effect of Daily Acetaminophen on Patients With Non-alcoholic Fatty Liver Disease (NAFLD) Compared to Healthy Controls
In this first pilot study, we will examine the effects of acetaminophen dosing in adult
patients with NAFLD in comparison to the effects in a healthy control group. Both groups
will receive 3 grams (g) of acetaminophen, the maximum recommended daily dose, daily for 14
days. We hypothesize that NAFLD patients are more prone to APAP toxicity than normal
controls.Treatment will be stopped after two weeks or in the following conditions:
Treatment with APAP will be stopped in healthy volunteers if ALT and/or AST reached three
times the ULN. In patients with NAFLD, treatment will be stopped if: ALT or AST reach ≥
three times the upper limit of entry value or ≥ 5 times the ULN; or if there is ALT or AST
>3 times ULN and TBili >2xULN or INR >1.5; or if there is ALT or AST >3 times ULN with the
appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever,
rash, and/or eosinophilia (>5%). We follow a conservative approach derived from the FDA
guidelines for stopping medications expected to cause drug induced liver injury (DILI).
Indeed, the FDA allows continuation of the medication until ALT or AST are >8x ULN in the
absence of elevated Tbili or INR. Patients who have hepatotoxicity will have close
monitoring of their liver enzymes until they normalize. Taking acetaminophen up to 3g daily
has been shown to be safe and acceptable. We have followed very strict criteria for
monitoring and stopping rules however in the usually cases of toxicity the patient will be
admitted for monitoring.
patients with NAFLD in comparison to the effects in a healthy control group. Both groups
will receive 3 grams (g) of acetaminophen, the maximum recommended daily dose, daily for 14
days. We hypothesize that NAFLD patients are more prone to APAP toxicity than normal
controls.Treatment will be stopped after two weeks or in the following conditions:
Treatment with APAP will be stopped in healthy volunteers if ALT and/or AST reached three
times the ULN. In patients with NAFLD, treatment will be stopped if: ALT or AST reach ≥
three times the upper limit of entry value or ≥ 5 times the ULN; or if there is ALT or AST
>3 times ULN and TBili >2xULN or INR >1.5; or if there is ALT or AST >3 times ULN with the
appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever,
rash, and/or eosinophilia (>5%). We follow a conservative approach derived from the FDA
guidelines for stopping medications expected to cause drug induced liver injury (DILI).
Indeed, the FDA allows continuation of the medication until ALT or AST are >8x ULN in the
absence of elevated Tbili or INR. Patients who have hepatotoxicity will have close
monitoring of their liver enzymes until they normalize. Taking acetaminophen up to 3g daily
has been shown to be safe and acceptable. We have followed very strict criteria for
monitoring and stopping rules however in the usually cases of toxicity the patient will be
admitted for monitoring.
NAFLD patients:
Inclusion criteria:
1. "Presence of NAFLD": This will be defined by the presence of at least two of the
following criteria: (a) suggestion of liver fat by an imaging study (ultrasound, CT
scan, MRI or MR spectroscopy) performed in the 6 months prior to enrollment; (b)
elevated aminotransferase levels (ALT > 31 U/L for men or > 19 U/L for women, or AST
> 30 U/L) on at least two occasions in the 6 months preceding enrollment; and (c)
presence of the metabolic syndrome, defined according to the modified AHA/NCEP
criteria. Biopsies are not required; however, previous biopsy done within the 6
months prior to the initiation of the study will be considered diagnostic if typical
findings of NAFLD are described and other causes of liver disease are ruled out;
2. Individuals who are 18-70 years old;
3. Written informed consent.
Exclusion criteria:
1. Serum ALT > 3 times ULN at baseline.
2. Evidence of another form of liver disease including viral hepatitis, autoimmune
hepatitis, cholestatic liver disease, Wilson's disease, Alpha-1-antitrypsin
deficiency, hemochromatosis or DILI.
3. History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day)
in the previous 10 years, or history of alcohol intake averaging greater than 10
gm/day (1 drink per day: 7 drinks per week) in the previous one year.
4. Evidence of liver cirrhosis on labs or imaging.
5. History of gastrointestinal bypass surgery or ingestion of drugs known to produce
hepatic steatosis in the previous 6 months.
6. Significant systemic or major illnesses other than liver disease.
7. Positive test for anti-HIV.
8. Active substance abuse.
9. Pregnancy or inability to practice adequate contraception in women of childbearing
potential
10. Evidence of hepatocellular carcinoma.
11. Any other condition which, in the opinion of the investigators, would impede
competence or compliance.
12. Serum creatinine >1.5 mg/dl.
13. Starting medications that have been shown to cause drug induced liver injury (eg,
augmentin, statins.) within one month prior to enrollment. Medications that have been
known to cause DILI but have taken for more than one month prior to enrollment (such
as statins) should not be an exclusion.
Healthy Controls:
Inclusion criteria:
1. Individuals who are 18-70 years old
2. Normal Liver enzymes
3. Negative hepatitis B surface antigen, and hepatitis C antibody
4. BMI (18.5 - 24.9) kg/m2
5. Written informed consent.
Exclusion criteria:
1. Presence of the metabolic syndrome, defined according to the modified AHA/NCEP
criteria
2. Taking concomitant medications
We found this trial at
3
sites
Click here to add this to my saved trials
Click here to add this to my saved trials
Click here to add this to my saved trials