No registrations found.
Source
Brief title
Health condition
Hepatocellular Adenoma (HCA), an uncommon, solid, benign liver lesion. Typically, it is a solitary lesion found in young women within their reproductive years.
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Our main study endpoint is the difference in tumour regression. The size (largest diameter in cm) of the largest hepatocellular adenoma found on MRI will be measured at T0 = time of inclusion and at T5= 6 months after start of the intervention. Mean regression will be calculated after which it will be compared to the regression in tumour size of our (earlier acquired) cohort.
Secondary outcome
Quality of Life, change in body weight, body composition, resting energy expenditure and plasma parameters.
Background summary
Rationale:
Hepatocellular adenoma (HCA) is an uncommon, solid and benign liver lesion. Typically, it is a solitary lesion found in women within their reproductive years and it is strongly associated with the use of oral contraceptive medication (OC). Development of HCA is also associated with obesity and metabolic syndrome. More recently, studies have shown a rising incidence of HCA diagnosis, current prevalence is estimated to be between 0.001 and 0.004%. HCA consists off several subtypes: inflammatory, steatotic, β-catenin mutation associated and unspecified. A higher BMI is associated with inflammatory HCA, which is also associated with multiple lesions. Steatotic HCA more often consist of single lesions.
Management of HCA requires a multidisciplinary approach. For female patients, it depends on the associated symptoms, lesion size and location. All female patients are advised to stop using OC and maintain a healthy body weight. Women with HCA can be included in a surveillance period (“Wait-and-see”-strategy) for 6 months, after which a contrast-enhanced magnetic resonance imaging (MRI) is performed. The aim is to predict if larger lesions (>5cm) will regress, thus avoiding unnecessary surgery. Treatment modalities to further enhance the regression and avoid surgery are an interesting research possibility. As overweight is frequently observed in women with liver adenoma, metabolic changes are assumed to play a role and diet may help to reduce tumour size.
Dietary restriction, defined as reduced intake of food without malnutrition, may be effective. It’s associated with metabolic changes, extended life span, lower risk of age associated diseases, improved fitness and increased resistance to acute stress. In combination with a ketogenic diet, it also reduces portal insulin concentrations, which down-regulate hepatic growth hormone receptors and reduces IGF-I synthesis. A recent study also shows the beneficial effect of eucaloric very-low-carbohydrate diet on disease control of acromegaly patients. Dietary restriction can be performed in different regimens such as short-term fasting or up to 30% reduced daily calorie intake. To explore the potential efficacy of dietary restriction, we aim to investigate whether the beneficial effects of a ketogenic diet with slight caloric restriction might increase the regression of HCA. This will further strengthen the treatment modality of close observation and avoid surgical resection.
Objective: to determine the effect of dietary restriction and the ketogenic diet on the regression of hepatocellular adenoma after 6 months.
Study design: A single-centre matched cohort study
Study population: Female subjects with a hepatocellular adenoma, who are entering a surveillance period including cessation of oral contraceptive medication and regular dietary advice. The main study population consists of female subjects who enter the first surveillance period of 6 months after diagnosis including cessation of oral contraceptive medication, the sub-population consists of female subjects who are subjected to another surveillance period of 6 months after having had no to minimal regression of their HCA during the first surveillance period.
Intervention: a ketogenic diet with +/- 30% less calories (approximately 35gr carbohydrate/ 1500 kcal per day) for 3 months, followed by a less strict ketogenic diet for 3 months (approximately 60gr carbohydrate/ 1500 kcal per day)
Main study parameters/endpoints:
The difference in regression of the liver adenoma after 6 months compared to historical controls and the feasibility / adherence of the dietary intervention. Other secondary endpoints are Quality of Life, change in body weight, body composition, resting energy expenditure and plasma parameters.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The extent of the burden of our study is considered low. Dietary restriction and the ketogenic diet have been proven feasible and safe in previous studies. For this study, three extra blood samples by 3 venous punctures are taken. No extra visits to the hospital or imaging studies are needed in order to obtain all the information required for this study. Several standardized questionnaires are asked to be filled in during and after the diet. Mentioned questionnaires take about 10 minutes to complete. No other risks concerning the dietary intervention are to be expected.
Study objective
We aim to investigate whether the beneficial effects of a ketogenic diet with moderate caloric restriction might increase the rate of regression of HCA.
Study design
T0 = time of inclusion, T3 = 3 months after start of the interventio and at T5 = 6 months after start of the intervention
Intervention
All subjects will receive a diet for 6 months (see table 1 & 2 for the example diet). In this ketogenic diet the amount of carbohydrates is restricted, the first three months to approximately 35 grams per day, the second part for month 4-6 to approximately 60 grams per day.
Month 1-3: Low carbohydrate, ketogenic diet containing approximately 1500 kcal, 35 grams of carbohydrate and 0.8 g/kg of protein /day
Month 4-6: Moderate carbohydrate, ketogenic diet containing approximately 1500 kcal, 60 grams of carbohydrate and 0.8 g/kg of protein /day.
C.A.J. Oudmaijer
010-7031810
c.oudmaijer@erasmusmc.nl
C.A.J. Oudmaijer
010-7031810
c.oudmaijer@erasmusmc.nl
Inclusion criteria
- Age 18-50 years
- BMI > 25 kg/m2
- Provide written consent
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Current pregnancy or breastfeeding
- Diabetes Mellitus type 1 or 2
- Insufficient understanding of the Dutch language
- Participation in another clinical study
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
NTR-new | NL9092 |
Other | METC Erasmus MC : MEC-2020-0777 |