Long Term Effect of Very-low-calories Ketogenic Diet on Weight Control and Cardiovascular Brisk Factors (KETOHEART)

NCT05781269 | Active Not Recruiting

• 1 other identifier: 43J001
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The growing obesity pandemic has a major impact on global cardiovascular (CVD)-related morbidity and premature mortality, severely compromising the quality of life of those affected and significantly increasing costs for the healthcare system. Numerous scientific evidences have demonstrated that a moderate weight loss (5-10% of the initial body weight) is already sufficient to determine the improvement of the cardiometabolic risk factors associated with overweight and obesity. With a view to obtaining a more significant weight loss in the initial stages of dietary treatment, in the last 10 years, the very low-calorie ketogenic diet (VLCKD) has become a strategy for the treatment of obesity and its comorbidities, also allowing to limit therapeutic failure and the high drop-out typical of traditional low-calorie diets. The present study aims to study the long-term efficacy (36 months) of VLCKD in patients with severe obesity and metabolic syndrome, on weight loss, on single factors of the metabolic syndrome compared to a restrictive Mediterranean diet. One hundred subjects with severe obesity and metabolic syndrome will be recruited and randomly assigned to VLCKD or to restrictive Mediterranean diet. Anthropometric parameters, metabolic status blood pressure, degree of arterial stiffness, prevalence and severity of snoring and OSA, cardiac systolic and diastolic function, the autonomic nervous control mode of the circulation will be evaluated at baseline, after one month and at the end of the study.

Conditions

Obesity; Morbid Obesity

Keywords

VLCKD; obesity; metabolic syndrome; cardiovascular risk

Outcome Measures

Primary Outcomes (6)

• change from baseline body weight at 36 months

  body weight measured to the nearest 0.1 Kg with a calibrated weight scale

  baseline, 36 month

• change from baseline fasting glucose in mg/dl at 36 months

  blood chemistry tests for the evaluation of blood glucose

  baseline, 36 month

• change from baseline HDL cholesterol, triglycerides at 36 months

  blood chemistry tests for the evaluation of HDL cholesterol, triglycerides

  baseline, 36 month

• change from baseline blood pressure in mmHg at 36 months

  measurement of systolic and diastolic pressure using using an aneroid sphygmomanometer with the appropriate cuff

  baseline, 36 months

• change from baseline distensibility of the carotid, radial and femoral arteries in m/s at 36 months

  arterial stiffness measured by Pulse Wave Velocity carotid-femoral

  baseline, 36 months

• change from baseline waist circumference in cm at 36 months

  waist circumference using a non-stretch tape to the nearest 0.5 cm

  baseline, 36 months

Secondary Outcomes (6)

• change from baseline total and LDL cholesterol in mg/dl at 36 months

  baseline, 36 months

• change from baseline % of subjects with obstructive sleep apnea at 36 months

  baseline, 36 months

• change from baseline cardiac systolic and diastolic function at 36 months

  baseline, 36 months

• change from baseline autonomic nervous control mode of the circulation at 36 months

  baseline, 36 months

• change from baseline insulin in mU/ml at 36 month

  baseline, 36 months

Study Arms (2)

VLCKD-group

EXPERIMENTAL

The VLCKD will be applied with the specific products of the ketogenic protocol supplied by Laboratoire Therascience starting from the Active Phase. During this phase the patients will take 4-6 LIGNAFORM products which will be followed by the Selective Phase in which in one or both of the main meals the LIGNAFORM product will be replaced with a protein dish and the phases of reintroduction of fruit (phase three), dairy products and legumes (phase four), bread and derivatives (phase five) and cereals (phase 6). At the end of the previous phases, a normocaloric maintenance diet will be set, with a carbohydrate intake not exceeding 45% of total daily calories. In these subjects, VLCKD diet will be maintained for 2 weeks every 2 months of maintenance diet.

Other: VLCKD

r-MedDiet

EXPERIMENTAL

The dietary treatment of the r-MedDiet group will provide for an average caloric deficit equal to 1000 kcal of the estimated total daily energy expenditure starting from the basal metabolic rate measured with indirect calorimetry and multiplied by the level of physical activity (LAF) defined on the basis of the Godin questionnaire. The diet will be personalized in 3 or 5 meals/day. Upon reaching the target weight, a Mediterranean-type diet plan will be set with a caloric intake equal to the estimated energy requirement

Other: r-MedDiet

Interventions

VLCKD OTHER

VLCKD diet treatment with medical food

VLCKD-group

r-MedDiet OTHER

Mediterranean diet treatment

r-MedDiet

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men between the ages of 55 and 75 with no documented history of CVD (except NYHA class I and II heart failure or valvular heart disease)
• Women aged 60 to 75, with no documented history of CVD (except NYHA class I and II heart failure or valvular heart disease)
• BMI ≥30 and \<50kg/m2-At least three positive factors for metabolic syndrome according to the harmonized definition (IDF --------2009)
• Availability to be followed in the follow-up at the San Michele Hospital IRCCS Istituto Auxologico Italiano in Milan

You may not qualify if:

• Long QT \>0.44 s, known arrhythmia, cardiomyopathy, heart failure (NYHA classes III-IV)
• Hypokalemia, hypernatremia
• Persistent diarrhea
• Acidosis (metabolic or respiratory) even if compensated
• Acute heart failure, transient ischemic attack or stroke in the previous 12 months
• Pregnancy or breastfeeding
• chronic renal insufficiency (creatinine \>1.5 and/or creatinine clearance \<45 mL/min), history -positive for previous episodes of acute renal failure
• Autoimmune diseases (TCA relative contraindication)
• History of previous pancreatitis
• Symptomatic cholelithiasis
• Hepatic insufficiency and/or ALT and AST \> 3 times the upper limit
• Stubborn constipation or history of intestinal occlusions/subocclusions
• Type 1 diabetes
• History of previous cancer within the first 5 years of follow-up
• Active eating disorder or history of bulimia and anorexia nervosa, active severe binge eating,

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead

Study Sites (1)

Istituto Auxologico Italiano

Milan, 20145, Italy

Location

Related Publications (6)

• Zomer E, Gurusamy K, Leach R, Trimmer C, Lobstein T, Morris S, James WP, Finer N. Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta-analysis. Obes Rev. 2016 Oct;17(10):1001-11. doi: 10.1111/obr.12433. Epub 2016 Jun 21.

  PMID: 27324830 BACKGROUND

• Diabetes Prevention Program Research Group; Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, Brown-Friday JO, Goldberg R, Venditti E, Nathan DM. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009 Nov 14;374(9702):1677-86. doi: 10.1016/S0140-6736(09)61457-4. Epub 2009 Oct 29.

  PMID: 19878986 BACKGROUND

• Look AHEAD Research Group; Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010 Sep 27;170(17):1566-75. doi: 10.1001/archinternmed.2010.334.

  PMID: 20876408 BACKGROUND

• Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, Hill JO, Brancati FL, Peters A, Wagenknecht L; Look AHEAD Research Group. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011 Jul;34(7):1481-6. doi: 10.2337/dc10-2415. Epub 2011 May 18.

  PMID: 21593294 BACKGROUND

• Caprio M, Infante M, Moriconi E, Armani A, Fabbri A, Mantovani G, Mariani S, Lubrano C, Poggiogalle E, Migliaccio S, Donini LM, Basciani S, Cignarelli A, Conte E, Ceccarini G, Bogazzi F, Cimino L, Condorelli RA, La Vignera S, Calogero AE, Gambineri A, Vignozzi L, Prodam F, Aimaretti G, Linsalata G, Buralli S, Monzani F, Aversa A, Vettor R, Santini F, Vitti P, Gnessi L, Pagotto U, Giorgino F, Colao A, Lenzi A; Cardiovascular Endocrinology Club of the Italian Society of Endocrinology. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE). J Endocrinol Invest. 2019 Nov;42(11):1365-1386. doi: 10.1007/s40618-019-01061-2. Epub 2019 May 20.

  PMID: 31111407 BACKGROUND

• Esposito K, Kastorini CM, Panagiotakos DB, Giugliano D. Mediterranean diet and weight loss: meta-analysis of randomized controlled trials. Metab Syndr Relat Disord. 2011 Feb;9(1):1-12. doi: 10.1089/met.2010.0031. Epub 2010 Oct 25.

  PMID: 20973675 BACKGROUND

MeSH Terms

Conditions

Obesity; Obesity, Morbid; Metabolic Syndrome

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Officials

• Simona Bertoli, MD

  Istituto Auxologico Italiano

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2023
• First Posted: March 23, 2023
• Study Start: February 20, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-09

Locations

IT (1)