Preoperative Ketogenic Diet for Reduction of Hepatic Steatosis

NAFLD Clinical Trial

Official title:

Implementation of a Preoperative Ketogenic Diet for Reduction of Hepatic Steatosis Prior to Hepatectomy: a Randomized Control Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05884723
• Other study ID #: 122435
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: July 2030

Study information

• Verified date: April 2024
• Source: Western University, Canada
• Contact: Anton Skaro, MD PhD
• Phone: 519-685-8500
• Email: Anton.Skaro[@]lhsc.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Non-alcoholic fatty liver disease is becoming increasingly common in Canada and throughout the world. Fatty liver can increase the risks of perioperative complications for those who need liver surgery. A ketogenic diet is low in carbohydrates and can be very effective in reducing liver fat content. The purpose of this randomized control trial is to compare the effect of a short duration (4 week) preoperative ketogenic diet on operative and disease outcomes in patients undergoing liver surgery. One arm will be randomized to the ketogenic diet and the other will receive standard of care pre-operative dietary consultation.

Description:

The rise in obesity has contributed to increasing rates of non-alcoholic fatty liver disease (NAFLD) in Canada and globally. In the setting of liver surgery, fatty liver has been associated with higher rates of blood loss during surgery as well as higher rates of postoperative complications. A pre-operative ketogenic diet (KD) has been proposed as a strategy to decrease the risks of fatty liver in patients undergoing liver surgery and has shown promising results in reducing liver fat content, even with short-duration diets. The current literature contains a large variety of pre-operative diets aimed at reducing liver fat content and most studies are observational. Presently, there is no randomized control trial looking at the effects of a well-formulated and standardized KD prior to liver surgery and its effect on operative and disease outcomes. This study will randomize patients with NAFLD needing surgery to remove liver tumors to either the control group or intervention group. Patients in the control group will receive dietary consultation for a standard of care diet as recommended by Canada's Food Guide. Patients in the intervention group will consult with a dietician before starting a 4-week preoperative well-formulated very low carbohydrate KD. All participants will track daily nutritional intake and provide weekly summary reports via an app called Cronometer. The investigators will analyze differences in intraoperative blood loss and OR time, postoperative complications, disease recurrence and mortality rates between the two groups.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 124
• Est. completion date: July 2030
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients 18 years of age or older undergoing any type of liver resection (e.g. wedge, formal hepatectomy), either open or laparoscopic, for colorectal liver metastases (CRLM)
• Patients with evidence of hepatic steatosis on pre-operative imaging (CT or MR) or biopsy.
• Ability to use an app based nutritional program to track macronutrient uptake throughout the dietary intervention.

Exclusion Criteria:

• Patients undergoing liver resection for any other indication
• Patients on sodium glucose co-transporter 2 (SGLT-2) inhibitors (these are contraindicated with a ketogenic diet).
• Patients without evidence of hepatic steatosis.
• Patients with evidence of liver fibrosis or cirrhosis on preoperative bloodwork or imaging.
• Patients with alcohol-related hepatic steatosis.
• Patients with a known bleeding disorder.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Metastasis Colon Cancer
• Liver Steatoses
• NAFLD
• Neoplasm Metastasis

Intervention

Dietary Supplement:
• Ketogenic Diet
4-week preoperative well-formulated very low carbohydrate isocaloric diet consisting of 50g net daily carbohydrates and 1.5g/kg protein with the remaining energy needs consisting of primarily mono- and polyunsaturated fats

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Western University, Canada

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Perioperative blood transfusion	receipt (binary) of packed red blood cell (pRBC) units intraoperatively and during the immediate postoperative time period (POD 0 - 7)	postoperative days 0-7
Secondary	Amount of perioperative blood transfusion	Number of pRBC units transfused	postoperative days 0-7
Secondary	Intraoperative blood loss	Intraoperative blood loss: measured by net sponge weight and fluid suctioned minus irrigation fluid	Operative period
Secondary	Steatosis	Level of steatosis in liver resection specimen	Time of primary surgery
Secondary	Change in steatosis	Change in steatosis in liver pre-diet vs day of surgery	~6 weeks
Secondary	Operative time	time from surgery start to surgery stop	During primary surgery
Secondary	Postoperative complications	Postoperative complications (measured via the Clavien-Dindo Index) will be assessed within 30 days of the operation.	Postoperative days 0-30
Secondary	Postoperative length of hospital stay	Postoperative length of hospital stay will be assessed.	Postoperative days 0-30
Secondary	Postoperative hospital readmission	Hospital readmission will be assessed within 30 days of the operation	Postoperative days 0-30
Secondary	Postoperative rates of reoperation	Reoperation rates will be assessed within 30 days of the initial surgery.	Postoperative days 0-30
Secondary	Postoperative liver failure	Liver failure rates will be assessed within 30 days of the initial surgery.	Postoperative days 0-30
Secondary	Postoperative mortality	Mortality rates will be assessed within 30 days of the initial surgery.	Postoperative days 0-30
Secondary	Adherence to ketogenic diet	whether participants adhered to the diet assigned to them	4 weeks
Secondary	Disease recurrence	Time to disease recurrence will be assessed up to 5 years postoperatively.	0 - 5 years postoperatively
Secondary	Measurement of circulating cell-free tumor DNA	Circulating cell-free tumour DNA levels will be measured up to 5 years postoperatively.	0 - 5 years postoperatively
Secondary	Cancer-related mortality	Cancer-related mortality rates will be assessed up to 5 years postoperatively.	0 - 5 years postoperatively