Adherence and Tolerability of Four Very Low-Calorie Ketogenic Diet Approaches in Adults With Obesity or Complicated Overweight (KOBE)

April 28, 2026 updated by: Maria Letizia Petroni, University of Bologna

KOBE Study: Adherence to and Tolerability of Different Very-low-calorie Ketogenic Protocols in Patients With Obesity and Complicated Overweight.

This study, called KOBE Study, looks at how well different very low-calorie ketogenic diets (VLCKD) are followed and tolerated by adults with obesity or complicated overweight in routine clinical practice.

Ketogenic diets are medical nutrition therapies that greatly reduce carbohydrates and calories to promote weight loss and improve metabolic health. Several VLCKD approaches are used in clinical care, but they differ in the type of protein sources used (natural foods versus meal replacements or supplements). At present, there is limited evidence comparing these approaches in terms of adherence, side effects, satisfaction, and dropout rates.

The KOBE Study is a single-center, prospective, observational study conducted during standard clinical care at a hospital nutrition clinic. Participants choose one of four VLCKD protocols based on personal preference:

  • diets using only natural protein foods,
  • natural proteins plus one protein supplement,
  • natural proteins plus two meal replacements,
  • or diets based entirely on meal replacements.

All participants follow the same structured program lasting about 26 weeks (longer for individuals with severe obesity), consisting of:

  1. an initial ketogenic phase,
  2. a gradual reintroduction of carbohydrates,
  3. a maintenance phase based on a low-glycemic index Mediterranean-style diet. Throughout the study, patients undergo routine clinical visits and assessments, including measurements of body weight, body composition, blood tests, liver imaging, and questionnaires on hunger, bowel habits, quality of life, and satisfaction with the diet. No additional tests beyond standard care are required.

The main goal of the study is to compare the different ketogenic protocols in terms of:

  • how well patients can follow them,
  • how well they are tolerated,
  • the occurrence of side effects,
  • and overall satisfaction. Secondary objectives include evaluating changes in body composition, metabolic parameters, and liver health.

The results of this study aim to help patients and healthcare professionals make more informed, evidence-based decisions when choosing among different ketogenic diet options for weight management and metabolic disease.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

110

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • BO
      • Bologna, BO, Italy, 40138
        • S.Orsola-Malpighi Hospital-University of Bologna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The target population includes all consecutive individuals who, in the context of routine clinical practice, meet the eligibility criteria for VLCKD therapy.

Description

Inclusion Criteria:

  • Obesity with or without comorbidities (BMI ≥ 30 kg/m²) OR
  • Overweight with comorbidity of MASLD (BMI 25.0-29.9 kg/m²) PLUS
  • Previous unsuccessful attempt at a prescribed hypocaloric diet

Exclusion Criteria:

  • Age < 18 years
  • Pregnancy
  • Breastfeeding
  • Moderate or severe kidney failure
  • Cardiovascular diseases: heart failure (NYHA III-IV), unstable angina, acute coronary syndrome or stroke within the past 12 months, paroxysmal atrial fibrillation, any type of atrioventricular block, left bundle branch block
  • Liver diseases: Child-Pugh C, elevated transaminases with AST or ALT ≥ 5 times the upper limit of normal, INR ≥ 1.5, total bilirubin ≥ 2 mg/dL
  • Diabetes: type 1 diabetes mellitus, type 2 diabetes mellitus with insufficient pancreatic endocrine reserve (C-peptide < 0.8 ng/mL), type 2 diabetes mellitus on multiple daily insulin injections
  • Last attempt of VLCKD outside the research protocol within the past 12 months
  • Eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder
  • Psychiatric comorbidities, alcohol or substance dependence
  • Frail elderly patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Arm A
In arm A, protein intake was derived exclusively from natural food sources, with three or four daily meals according to individual energy and protein requirements. Protein sources included lean white meats (chicken, rabbit, turkey), lean red meats (veal and pork), lean and defatted cured meats (bresaola, cured and cooked ham), fish (gilthead seabream, cod, hake, trout), and 0% fat Greek yogurt.
Arm B
In arm B, the same natural food sources were combined with one daily meal, corresponding to breakfast, based on whey protein supplementation.
Arm C
In arm C, one or two daily meals, according to individual energy and protein requirements, consisted of natural foods, whereas the remaining two meals were provided as commercial meal replacement products.
Arm D
In arm D, all daily meals consisted exclusively of commercial meal replacement products.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adherence, collateral effects, drop-out, dietetic compliance
Time Frame: Until the end of the study

The primary objective of the study is to evaluate, within routine clinical practice and by comparing four distinct VLCKD protocols, the therapeutic response of patients in terms of:

(i) adherence (compliance), (ii) occurrence of adverse events, (iii) drop-out rate, and (iv) diet satisfaction.

The four ketogenic protocols routinely used in patients undergoing VLCKD each consist of three phases; only the first phase differs among protocols, based on patients' personal preferences.
Until the end of the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anthropometric Measures, Body Composition, Laboratory Parameters, and Imaging Evaluations
Time Frame: Until the end of the study

The secondary objectives are to evaluate the effects of the different VLCKD protocol arms on the trends of parameters collected during routine clinical practice, including:

(i) first- and second-level anthropometric measurements (body weight, Body Mass Index (BMI), and circumferences); (ii) body composition; (iii) biochemical laboratory tests according to the Società italiana di Endocrinologia (SIE) Consensus Statement, with particular attention to serum creatinine levels.

(iv) upper abdominal ultrasound and hepatic-splenic transient elastography assessed using the FibroScan technique.
Until the end of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Bologna

Collaborators

S. Orsola-Malpighi Hospital, University of Bologna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2021

Primary Completion (Actual)

August 20, 2024

Study Completion (Actual)

June 30, 2025

Study Registration Dates

First Submitted

January 28, 2026

First Submitted That Met QC Criteria

January 28, 2026

First Posted (Actual)

February 5, 2026

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 650/2021/Oss/AOUBo

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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