Clinical trial NCT02935478: Bariatric Embolization of Arteries in Obese Patients With HCC to Allow Salvage Liver Transplantation
Official title: A Single Center, Non-randomized Study to Evaluate the Safety and Efficacy of Left Gastric Artery Embolization in Obese Patients With Hepatocellular Carcinoma to Achieve Appropriate Weight Loss That May Allow Them to be Transplanted
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Obesity
Weight Loss
Body Weight
Hepatocellular Carcinoma
HCC
Hepatitis C
Cirrhosis
Keywords: bariatric surgery
minimally invasive
Embolization
ghrelin
gastric artery embolization
Lead sponsor: St. Louis University
Sponsor class: OTHER
First posted: 2016-10-17
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and has a grave prognosis. Obesity is an epidemic in the US.Patients with HCC and obesity are not candidates for liver transplantation, depriving them of the best option for cure from HCC.

Recent studies have shown that blocking blood vessels to a particular portion of the stomach (bariatric or left gastric artery embolization) can temporarily decrease levels of the appetite inducing hormone ghrelin, and result in weight loss.The purpose of this study is to determine if Left gastric artery embolization (LGAE) in patients with cirrhosis and HCC who are not transplant candidates due to morbid obesity, leads to clinically significant weight loss with eligibility for liver transplantation.

Detailed description: Obesity:In adults, obesity is defined as a BMI of greater than 30 kg/m2. It is estimated that, by the year 2030, 38% of the world's adult population will be overweight and another 20% obese .An expert panel convened by the NIH stated that for the first time in history, the steadily improving worldwide life expectancy could level off or even decline, as the result of increasing obesity.

Liver cirrhosis with portal hypertension and HCC:

The problem: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor seen in the setting of cirrhosis, which itself can be of varying etiology. NASH as cause for liver cirrhosis and HCC has been growing in last decade. Although Hepatitis C is currently the most common indication for liver transplant, longitudinal trends show that NASH has a trajectory to become the most common.

Current options in management: Patients who develop HCC in the context of underlying chronic liver disease complicated by portal hypertension are not candidates for resection therapy; rather, orthotopic liver transplantation (OLT) offers the best option for cure and long-term survival. Most transplant centers have strict criteria for OLT; one of the most common is a BMI \< 35 kg/m2. Most NASH patients with HCC will have a high BMI. Unfortunately in presence of HCC these patients have a very limited time to lose enough weight to qualify to be listed. Lifestyle modification and medical therapies are relatively ineffective. Bariatric surgery is contraindicated in patients with portal hypertension due to significant increase in post-operative mortality, more relevant in patient listed to liver transplantation.

Thus a safe and effective minimally invasive option is needed. Based on currently available data, Left gastric artery embolization (LGAE) appears effective in inducing weight loss of about 10.5% in 3-6 months, with a high safety profile. In patients who have cirrhosis and portal hypertension with HCC and who are not transplant candidates due to morbid obesity , appropriate and timely weight loss of 10.5% in 3-6 months by performing LGAE may allow them to be listed and transplanted before their cirrhosis and tumor reaches an inoperable stage( within Milan criteria). In patients with HCC, the procedure can be performed concurrently with the procedure of Trans arterial chemoembolization which is commonly used in down staging HCC to Milan criteria.

Eligibility criteria: Inclusion Criteria:

* Male or Female, aged 18 years or older.
* Willing, able and mentally competent to provide written informed consent and willing to comply with all study procedures and be available for the duration of the study
* BMI \>35 kg/m2
* Adequate hematological, hepatic and renal function as follows:

  * Hematological: Platelets \> 50 x 109/L, INR \<1.5
  * Hepatic : Total bilirubin \<3 mg/dL
  * Renal: Estimated GFR \> 60ml/min.1.73m2
* Clinical, laboratory and radiographic evidence (ultrasound/ CT/MRI) of cirrhosis of any etiology with portal hypertension and concomitant HCC (treated or untreated).
* Besides a BMI \>35 kg/m2, otherwise eligible for liver transplantation
* Suitable for protocol therapy as determined by the interventional radiology Investigator.

Exclusion Criteria:

* Pregnancy
* Active substance abuse
* Significant psychiatric problems, severe enough to cause suffering or a poor ability to function in life. Center for Epidemiological Studies Depression (CESD) score \< 16.
* Significant alcohol consumption ( \>20 g/day in women, \>30 g/day in men)
* Weight \> 400 lbs.
* Presence of systemic illness or other medical conditions relevant to survival .(Note that the presence of HCC will not be considered an exclusion criteria)
* Metastatic cancer
* Evidence of decompensated liver disease (uncontrolled ascites, or uncontrolled spontaneous encephalopathy)
* prior surgical weight loss procedures including gastroplasty, jejunoileal, or jejunocolic bypass, total parenteral nutrition within the past 6 months; Prior history of gastric pancreatic, hepatic, and/or splenic surgery
* Prior embolization to the stomach, spleen or liver.
* If review of available prior imaging studies (i.e. CT, MRI, or US) shows potential anatomical variations, presence of severe atheromatous disease, large arteriovenous shunting of blood.
* Abnormal Endoscopy - large sliding hiatal hernia or paraesophageal hernia, active peptic ulcer disease, active H. pylori infection
* History of abnormal Nuclear Gastric Motility examination-defined as delayed emptying of gastric contents \> 90%, 60% and 10% at 1 hour, 2 hours, and 4 hours respectively.
* ASA Class 4 or 5
* Child Pugh classification C

Primary outcomes:
measure: Weight
timeFrame: 12 months
Secondary outcomes:
measure: Clinical parameter- Abdominal circumference
timeFrame: 12 months
measure: Clinical parameter-Blood pressure
timeFrame: 12 months
measure: Laboratory parameter-Ghrelin and other serum obesity hormones(Leptin, GLP-1, PYY)
timeFrame: 12 months
measure: Laboratory parameter-serum glucose
timeFrame: 12 months
measure: Laboratory parameters- HbA1c
timeFrame: 12 months
measure: Laboratory parameters-Lipid profile
timeFrame: 12 months
measure: Number of patients with clinical adverse events
timeFrame: 12 months
measure: Number of patients with abnormal endoscopies
timeFrame: 12 months
measure: Eligibility for liver transplant
timeFrame: 12 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
Study officials:
affiliation: Assistant professor of radiology-Interventional radiology
name: Keith Pereira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Associate professor of radiology-Interventional radiology
name: Kirubahara Vaheesan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of internal medicine- Gastreoenterology
name: Alex Befeler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistant Professor of Surgery- abdominal transplant
name: Mustafa Nazzal, MD
role: PRINCIPAL_INVESTIGATOR
References:
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