The Effect of Pentoxifylline on Nonalcoholic Steatohepatitis (NASH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- The Number of Participants With a 30% Reduction in Alanine Aminotransferase (ALT) Treated With Pentoxifylline (PTX) or Placebo for 12 Months.
研究概览
简要总结
The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH.
详细描述
This is an investigational study looking at subjects who have been diagnosed with nonalcoholic steatohepatitis (NASH) or 'fatty liver disease'. There is currently no FDA approved available treatment for NASH. The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH. The effectiveness of this drug will be determined by taking blood samples and a liver biopsy. To determine if there is any effect of the medication, two-thirds of the patients participating in the study will receive pentoxifylline and one-third will receive placebo (sugar pill). Thus, an individual's chance of receiving the drug is 67%. In addition to receiving a study drug (placebo or pentoxifylline) the subjects will be encouraged to achieve modest weight loss (~1-2 lbs/week) via low-fat diet and exercise.
The drug (Pentoxifylline) being studied is not approved for use in people who have NASH. Pentoxifylline is considered experimental in this study. Pentoxifylline has been safely used for the treatment of other medical conditions such as alcohol related liver disease and poor circulation. Pentoxifylline is a pill which is taken three times a day.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be willing to give written informed consent
- •Diagnosis of steatohepatitis Grade >= 1 (Brunt et al. criteria - Am J Gastroenterology 1999;94(9)2467-74) on biopsy within 6 months prior to entry into protocol
- •No histologic evidence of cirrhosis
- •Persistent ALT elevation (> 1.5 the upper limit normal) over 6 months prior to entry into study
- •Adult subjects 18-65 years of age of any race or gender
- •Compensated liver disease with the following hematologic, biochemical, and serological criteria on entry into protocol:
- •Hemoglobin > 11 gm/dL for females and > 12 gm/dL for males
- •White blood cell (WBC) > 2.5 K/UL
- •Neutrophil count > 1.5 K/UL
- •Platelets > 100 K/UL
- •Direct bilirubin, within normal limits
- •Indirect bilirubin within normal limits (unless non-hepatitis factors such as Gilbert's disease explain indirect bilirubin rise. In such cases total bilirubin must be < 3.0 mg/dL)
- •Albumin > 3.2 g/dL
- •Serum creatinine within normal limits
- •Hemoglobin A1c (HgbA1c) < 7%
- •Antinuclear antibodies (ANA) < 1:160
- •Anti-smooth muscle Ab negative
- •Serum hepatitis B surface antigen (HepBsAg) negative
- •Serum hepatitis C antibody (HepC Ab) negative
- •Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) < 45%
- •Alpha-1-antitrypsin level within normal limits
- •Ceruloplasmin level within normal limits
- •Negative pregnancy test (females)
- •Concomitant use of lipid lowering agents at study entry will not exclude patients from the study.
排除标准
- •Evidence of decompensated cirrhosis
- •Active gastrointestinal (GI) bleeding
- •Renal failure (creatinine clearance < 80 mL/min)
- •Active alcohol or drug abuse
- •Uncontrolled diabetes (HgbA1c > 7)
- •Current treatment with anti-diabetic medications such as thiazolidinediones or metformin (stable doses of sulfonylureas are acceptable)
- •Current treatment with anti-TNF alpha medication (i.e. Remicade or Enbrel)
- •Current treatment with vitamin E
- •Alcohol consumption < 20 g/day (males) or < 10 g/day (females) - assessed by one physician and confirmed with one family member.
- •HIV positive status
- •Any history of cerebral and/or retinal hemorrhage
- •Prior intolerance of pentoxifylline or any other methylxanthine (i.e. caffeine, theophylline, or theobromine)
- •Current use of theophylline
- •Known diagnosis of malignancy
- •Any other conditions which the investigator feels would make the subject unsuitable for enrollment, or could interfere with the subject completing the protocol
研究组 & 干预措施
Pentoxifylline
400mg PO TID
干预措施: Pentoxifylline (Drug)
Placebo
1 pill PO TID
干预措施: Placebo (Drug)
结局指标
主要结局
The Number of Participants With a 30% Reduction in Alanine Aminotransferase (ALT) Treated With Pentoxifylline (PTX) or Placebo for 12 Months.
时间窗: baseline and 12 months
The primary goal of the study was to determine whether pentoxifylline (PTX) therapy improved serum ALT (\> or = 30% change from baseline to month 12) compared to placebo.
次要结局
- Change in Serum Adiponectin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months(one year)
- Change in Serum Leptin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months(baseline and one year)
- The Effect of Pentoxifylline on Change in Tumor Necrosis Factor [TNF]-α Levels in Patients With NASH(one year)
研究者
Mary Rinella
Mary E. Rinella, MD, Northwestern University
Northwestern University