Clinical trial NCT06850493: Ketogenic Diet Prior to Bariatric Surgery
Official title: The Impact of a Preoperative Very Low Calorie Ketogenic Diet (VLCKD) on Body Composition in Patients Undergoing Bariatric Surgery: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bariatric Surgery Candidate
Ketogenic Dieting
Lead sponsor: Maxima Medical Center
Sponsor class: OTHER
First posted: 2025-02-27
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Standard dietary regiments for bariatric are advised prior to surgery. The most used diet is a very low calorie diet (VLCD). These diets potentially have multiple pittfalls.

Very low-calorie ketogenic diets (VLCKD) have been proposed as a new regimen for achieving weight- and liver volume loss in patients undergoing bariatric surgery. The beneficial effect of VLCKDs compared to (V)LCDs is the aimed preservation of FFM and RMR, while still reducing FM. Only a few small studies addressed the role of VLCKDs prior to bariatric surgery, and the data including FFM and FM is actually scarce. Therefore, a well-designed randomised controlled trial is necessary to establish the efficacy of a VLCKD.

Detailed description: According to the World Health Organization, obesity rates have nearly tripled since 1975, resulting in the mortality of four million individuals each year. Obesity contributes to a reduced quality of life and is a significant risk factor for multiple chronic diseases such as type 2 diabetes mellitus, cardiovascular disease, osteoarthritis and certain types of cancer . Bariatric surgery is regarded the most effective treatment for extreme obesity because it achieves significant long-term weight loss and improves or even eliminates obesity-related complications. Based on the American Society for Metabolic and Bariatric surgery, approximately 230.000 bariatric procedures are performed annually, and those procedures predominantly included sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB) procedures. Bariatric surgery can be challenging because of an increased thickness of the abdominal wall, the presence of intra-abdominal obesity and hepatomegaly. These anatomical changes are associated with more anaesthetic and surgical manoeuvres during the procedure. Losing weight prior to the procedure is frequently advised because it may help to overcome technical challenges. It may furthermore improve short-term outcomes like surgical time, blood loss, hospital stay and postoperative complications, as well as long-term outcomes like weight loss.

In the preoperative phase, weight loss can be realised by multiple dietary regimens, including low-calorie diets (LCD) (800-1500 kcal/day) and very low-calorie diets (VLCD) (\<800 kcal/day). In Máxima Medical Center and a few other hospitals performing bariatric surgery in the Netherlands, the VLCD is the standard diet of choice, which begins two weeks prior to surgery. Systematic reviews reported, as result of these diets, a reduction in liver size (5-20% with a VLCD; 12-27% with a LCD), intrahepatic fat (43% with a VLCD; 40-51% with a LCD) and body weight (2.8-14.8kg with a VLCD; 5.4-23.6kg with a LCD). These diets varied in duration, from two weeks to four months. One of the primary drawbacks of these diets is the loss of metabolically active fat free mass (FFM) and lean body mass (LBM), which are crucial for whole-body protein metabolism, in addition to fat mass (FM). In contrast to FFM, LBM contains bone mass, connective tissue, internal organs and essential fat stored in these tissues. It has been hypothesised that LBM will contain 3 to 5% more fat than FFM. A significant loss of FFM may negatively affect the resting metabolic rate (RMR), slow the rate of weight loss and predispose weight regain in the long-term. A significant loss of FFM, in continuing presence of an excessive FM, may furthermore contribute to sarcopenic obesity. A second important downfall is that some patients may not tolerate a (V)LCD regime due to side-effects leading to poor compliance and subsequently poor weight loss outcomes. For clinical trials, the reported attrition rate for a (V)LCD regime is around 20%, raising concerns about the study validity.

Very low-calorie ketogenic diets (VLCKD) have been proposed as a new regimen for achieving weight- and liver volume loss in patients undergoing bariatric surgery. A VLCKD is characterized by a very low carbohydrate content (\<50 g/daily), a low-fat content (15-30 g fat/daily) and a high amount of proteins (1-1.5 g protein/kg ideal body weight). The beneficial effect of VLCKDs compared to (V)LCDs is the aimed preservation of FFM and RMR, while still reducing FM. In addition, the compliance of patients might be improved by VLCKDs, possibly due to the anorexigenic effect and hunger reduction of ketone bodies. Only a few small studies addressed the role of VLCKDs prior to bariatric surgery, and the data including FFM and FM is actually scarce. A retrospective cohort study found that a three-week lasting VLCKD resulted in more weight loss (5.8kg vs. 4.8kg) compared to a VLCD. In addition, two prospective cohort studies showed as result of a VLCKD, FFM was reduced by 7.6 kg (10.0%) and 0.7kg (1.1%) , whereas FM was reduced by 10.5kg (17.9%) and 5kg (8.8%). What is important to note is that these studies lack a control group, randomisation and are subjected to limitations in FFM and FM measurement due to the use of single-frequency bioelectrical impedance analysis (BIA). Therefore, a well-designed randomised controlled trial is necessary to establish the efficacy of a VLCKD.

Eligibility criteria: Inclusion Criteria:

* Eligible for bariatric surgery (≥35 kg/m2 with obesity-related comorbidities, or a BMI of

  * 40 kg/m2 with or without comorbidities)
* Roux-en-Y Gastric bypass (RYGB)

Exclusion Criteria:

* Weighing over 150kg because this amount is a limitation by the DXA device
* Diabetes mellitus type 1
* Allergic to milk proteins
* A recent history of a heart attack (\< 12 months), heart failure or cardiac arrhythmias
* Kidney and/or liver failure (creatinine levels \>1.3 mg/dl or liver enzyme levels (AST, ALT, GGT)) less than three times over the upper normal threshold
* Current infectious, sepsis or malignant disease
* Rare condition like galactosemia, phenylketonuria or porphyria
* Persistent diarrhoea
* Hypokalaemia, chronic therapies with diuretics as furosemide and hydrochlorothiazide
* Pregnancy or plans to get pregnant in the coming months
* Patients who did not meet criteria to be eligible for bariatric surgery (BMI \<35, psychological or unstable psychiatric disorders, inadequate dietary regimen or inadequate exercise pattern which can't be resolved in the upcoming 6 months)

Primary outcomes:
measure: Change in FFM (%) in proportion to TBWL
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
Secondary outcomes:
measure: Change in weight
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Physical activity questionnaire
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Patient satisfaction assessed by a questionnaire
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Incidence of side effects, assesed by questionnaire
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Compliance assesed by return of diet sachets
timeFrame: 2 weeks prior to surgery till the day of surgery
measure: Change in weight
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Upper extremity muscle strenght
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Surgical outcome (1)
timeFrame: Day of surgery
measure: Surgical outcome (2)
timeFrame: From day of surgery untill the day of discharge, counted as the nights a patient has stayed in the hospital for admission
measure: Surgical outcome (3)
timeFrame: Day of surgery up to 30 days postoperatively
measure: Surgical outcome (4)
timeFrame: Day of surgery up to 30 days postoperatively
measure: Biochemical testing- Ketosis
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Electrolytes- Sodium)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Electrolytes - Potassium)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Electrolytes - Albumin)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Liverfunction - Aspartate Aminotransferase (AST))
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Liverfunction - Alanine Transaminase (ALT))
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Liverfunction - Gamma glutamyl transpeptidase (GGT))
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Kidney function - Creatinine)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Kidney function - Urea)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Kidney Function - Estimated glomerular filtration rate (eGFR))
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Iron)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Hemoglobin)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Metabolic profile - Total cholesterol)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Metabolic profile - low-density lipoprotein (LDL))
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Metabolic profile - High-density lipoprotein (HDL))
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Metabolic profile - Triglycerides)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Calcium)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
measure: Biochemical testing (Glucose)
timeFrame: 2 weeks prior to surgery, day of surgery and 3 months after surgery
Other outcomes:
Locations:
city: Veldhoven
country: Netherlands
facility: Maxima Medical Center
state: Noord-Brabant
Study officials:
affiliation: Maxima Medical Center
name: Francois van Dielen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: