Pilot Study to Assess the Feasibility, Safety and Tolerability of Sleeve Gastrectomy in Morbidly Obese Patients Undergoing Orthotopic Liver Transplantation
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Northwestern University
- Enrollment
- 1
- Locations
- 2
- Primary Endpoint
- Safety of Sleeve Gastrectomy
Study Overview
Brief Summary
The rapid rise in obesity (body mass index (BMI) ≥ 30 kg/m2) in the US over the past decade is responsible for more disease and death than any other single factor. Severe obesity is associated with numerous co-morbidities contributing to increased mortality risk, including end stage liver disease. Liver transplantation is a life-saving procedure for patients with end stage liver disease and obesity is becoming increasingly prevalent in this population. In one study, 54% of patients undergoing orthotopic liver transplant (OLT) were either overweight or obese [body mass index (BMI) >25 kg/m2], and 7% were severely or morbidly obese (BMI > 35 kg/m2). In addition, weight gain after solid organ transplantation is common because of steroid-containing immunosuppression and physical inactivity from decreased exercise tolerance.
Obesity has been shown to increase the surgical morbidity, including wound infections, wound dehiscence, and hernias after transplantation. More significantly, excess pretransplant body weight hinders the rate of improvement in health-related quality of life after liver transplantation[7].
One possible approach for treating obesity after a liver transplant is to use bariatric surgery. Currently, bariatric surgery is established as the most effective means for both weight loss and resolution of metabolic disease in the morbidly obese. Recent publications emphasize the usefulness of bariatric surgery in the reduction of long-term cardiometabolic risk, cardiovascular disease incidence and mortality, and the management of uncontrolled type 2 diabetes (T2DM). In addition, it decreases mortality and improves both social functioning and quality of life.
Bariatric surgery may improve eligibility for transplant in patients previously excluded due to excessive weight. Bariatric procedures, such as sleeve gastrectomy, allow for significant weight loss over time that greatly reduces or eliminates obesity related illnesses such as diabetes, high blood pressure and liver disease.
According to the National Institutes of Health, bariatric surgery is reserved for patients with a BMI of > 40 or > 35 kg/m2 in the presence of major co-morbidities (e.g. type 2 diabetes, hypertension, sleep apnea, heart disease, etc).
A significant number of liver transplant candidates have obesity-related illnesses, thus putting them at risk for cardiovascular and metabolic complications post-transplant. In addition, patients awaiting OLT are typically no longer medically stable to undergo intensive diet and exercise regimens as treatment for their diseases. Finally, decreased activity and medications used to prevent liver graft rejection all contribute to increased weight gain following transplant. In fact, in a series of 320 non-obese liver transplant recipients, 21.6% of patients became obese within two years of transplant. These comorbidities also contribute to poorer post-transplant outcomes and development of what is known as the post-transplant metabolic syndrome. Morbidly obese patients (BMI > 40 kg/m2) may also have higher frequencies of morbidities such as prolonged hospitalization and readmission as well as infectious, wound, and cardiovascular complications after transplantation. Finally, intra-abdominal adiposity creates a technically more challenging operative dissection, but no data exist on whether it increases perioperative morbidity or mortality in liver transplant patients.
Sleeve gastrectomy is the most attractive restrictive procedure in a liver transplant population for several key reasons. One, sleeve gastrectomy does not require the implantation of a foreign body, such as placement of an adjustable gastric band, which in an immunocompromised post-transplant patient raises concern for severe infectious complications. Secondly, as stated previously, sleeve gastrectomy is a purely restrictive procedure, and therefore is least likely to cause significant macronutrient and micronutrient deficiencies. Finally, when compared to other restrictive procedures, such as adjustable gastric band placement, it has a lower likelihood of treatment failure (i.e. <50% excess weight loss). In fact, recent reports describe not only high failure rates with adjustable gastric band placement, but also high reintervention rates for both band-related complications (e.g. band erosion, leakage, slippage, port infection and esophageal dilatation) and failure to lose weight such that as few as 54% of patients may have their band in place after 10 years.
Detailed Description
PROCEDURAL DETAILS
A sleeve gastrectomy is performed with the patient in reverse Trendelenburg position. The liver is retracted cephalad and to the right, and the short gastric vessels of the greater curvature and retrogastric attachments are divided from the angle of His to approximately 6-8cm from the pylorus. A 30-40 French bougie is placed in the stomach and directed along the lesser curve. The antrum is preserved and a vertical subtotal, sleeve gastrectomy is then fashioned along the lesser curvature 1 cm away from the bougie toward the esophagogastric junction using linear staplers, beginning 6 cm from the pylorus on the greater curve side and continuing up to the angle of His. The staple line may be oversewn with a running absorbable suture or an absorbable staple buttress material may also be used to help prevent bleeding. Air is infused via an endoscope into the newly created "sleeve" to rule out a leak ([33]).
CLINICAL DATA TO DATE
Weight Loss Weight loss surgery has been shown to be a safe, effective and durable option for the treatment of morbid obesity.[34, 35] The primary weight loss effectiveness parameters measured are percent excess weight loss (%EWL), defined as the difference in the baseline and post-surgery weight divided by the difference in baseline weight and ideal body weight (based on the 1983 Metropolitan Tables for Life Insurance) multiplied by 100, and reduction in BMI. Studies on the early outcomes of sleeve gastrectomy report a mean EWL of 51-85% at 3 years and 43-58% after 6 years. [36, 37] Additionally, patients have been shown to reduce their (average) BMI more than 15 points in the first year. [38-40]
Improvements in Obesity-related conditions after bariatric surgery Patients undergoing sleeve gastrectomy experience a statistically significant (p<0.001) reduction in glycosylated hemoglobin (HbA1c). Over two-thirds of patients return to a HbA1c of 6.5% or less within a year. [41, 42] In addition, more than half of patients experience complete resolution of diabetes within one year. Blood pressure normalization is seen in 50-75% of patients who undergo gastric sleeve, and these rates are comparable with those of Roux en Y gastric bypass and adjustable gastric banding (AGB).[42] Hyperlipidemia, present in nearly half of patients undergoing sleeve gastrectomy, has also shown a resolution rate of nearly 100%.[43]
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects must be willing to give written informed consent.
- •Adult subjects 18-75 years of age of any race or gender who are listed for liver transplantation.
- •For consideration of sleeve gastrectomy placement patients must meet the following criteria:
- •Class III Obesity (BMI ≥ 40 kg/m2); or
- •Class II Obesity (BMI 35-39.9 kg/m2 in conjunction with any of the following severe obesity related co-morbidities): i. Obstructive sleep apnea defined as a formal sleep study consistent with this diagnosis with a) an Epworth sleepiness scale ≥ 6 and b) polysomnography with respiratory disturbance index ≥ 10 and/or apneic episodes per hour of sleep; or ii. Cardiovascular disease defined as prior history of stroke, myocardial infarction, stable or unstable angina pectoris, or prior coronary artery bypass); or iii. Medically refractory hypertension defined as blood pressure greater than 140 mmHg systolic and/or 90 mmHg diastolic despite concurrent use of 3 anti-hypertensive agents of different classes iv. Type 2 diabetes mellitus, defined as individuals taking insulin or oral hypoglycemic agents or who have a fasting glucose > 126 mg/dL
- •Have attempted (and failed) previous weight loss efforts over at least a three month period with diet, exercise, lifestyle changes or medications.
- •Show understanding of the risks and benefits of surgery and side effects of the procedure.
- •Be committed to lifestyle changes. All patients will be evaluated by the transplant psychologist as well as the bariatric surgery psychologist prior to consideration for study enrollment to ensure appropriate psychological motivation.
- •Do not have any medical, psychiatric or emotional condition that would prohibit surgery (e.g. severe irreversible coronary artery disease, untreated schizophrenia, active substance abuse, and/or noncompliance with previous medical care)
Exclusion Criteria
- •Status 1 listing (fulminant hepatic failure) for liver transplant
- •Active drug abuse or alcohol use within six months
- •Positive urine pregnancy test (females)
- •Diagnosis of active malignancy
- •History of prior bariatric surgery
- •Failure to attend the initial patient information sessions or history of noncompliance
- •Failure to give consent for the study or to understand the proposed consent
- •Failure of patient's insurance company to approve surgical intervention so as to avoid extensive cost burden on the patient
Outcomes
Primary Outcomes
Safety of Sleeve Gastrectomy
Time Frame: Expected duration of subject participation is 1 year
The primary endpoint is the safety of sleeve gastrectomy during liver transplant as measured by adverse event rates, infectious complications and length of hospital stay compared to UNOS and institutional data.
Secondary Outcomes
- Weight Loss(6 months after transplant)
Investigators
Mary Rinella
Principal Investigator
Northwestern University