Vey Low-Energy Ketogenic Therapy in Adults With Type 1 Diabetes and Obesity on Intensive Insulin Therapy Using Advanded Hybrid Closed Loop System

NCT07185555 | Recruiting

• 1 other identifier: 1835/CEL
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Overweight and obesity are frequent in adults with type 1 diabetes (T1D), with prevalence exceeding 50% in recent studies. Excess weight in T1D is associated with higher cardiometabolic risk and therapeutic challenges, while effective and safe weight management strategies are still limited. This single-center, single-arm feasibility study will evaluate the efficacy and safety of a Very Low-Energy Ketogenic Therapy (VLEKT; 600-800 kcal/day) in adults with T1D and obesity treated with Advanced Hybrid Closed Loop (AHCL) insulin delivery systems. Participants will follow a structured 4-week program with commercial very-low-carbohydrate, high-protein meal replacements, under close medical supervision. The primary endpoint is change in body weight at 4 weeks. Secondary outcomes include body composition, muscle strength, glucose metrics, insulin requirements, biochemical parameters, and patient-reported outcomes. Safety will be assessed through hypoglycemia incidence, ketone monitoring, and occurrence of diabetic ketoacidosis (DKA). The study will enroll 14 participants. It is expected that VLEKT will achieve \~5% weight loss within one month while maintaining glycemic safety under AHCL technology.

Conditions

Type 1 Diabetes (T1D); Obesity (Disorder)

Keywords

Type 1 Diabetes Mellitus; Obesity; Very Low-Energy Ketogenic Diet; Insulin Therapy; Weight Loss; Continuous Glucose Monitoring; Advanced Hybrid Closed Loop

Outcome Measures

Primary Outcomes (1)

• Change in body weight from baseline to end of 4-week Very Low-Energy Ketogenic Therapy

  Body weight will be measured in kilograms using a calibrated scale at baseline and after completion of the 4-week intervention. The primary outcome is the absolute change in weight from baseline. Participants will be assessed under standardized conditions (light clothing, no shoes, fasting state where possible).

  Baseline and Week 4

Study Arms (1)

Very Low-Energy Ketogenic Therapy with Advanced Hybrid Closed Loop in Adults with T1D and Obesity

EXPERIMENTAL

Participants will undergo a 4-week Very Low-Energy Ketogenic Therapy (600-800 kcal/day) using commercial meal replacements with very low carbohydrate content, high biological value proteins (milk, whey, pea, soy), and added fiber (inulin, FOS). Gluten-free, lactose-free, and vegan options will be available. Therapy will be performed while continuing intensive insulin treatment with an Advanced Hybrid Closed Loop (AHCL) system. Participants will perform daily self-monitoring of capillary ketonemia, maintain hydration, and abstain from intense exercise. Follow-up visits at weeks 1, 2, 3, and 4 will assess safety, metabolic control, and weight loss. After completion, a structured reintroduction of conventional meals will be initiated.

Dietary Supplement: VLEKT

Interventions

VLEKT DIETARY_SUPPLEMENT

Participants will follow a Very Low-Energy Ketogenic Therapy (VLEKT) providing 600-800 kcal/day for 4 weeks. The intervention consists of meal replacements (solid or liquid, ready-to-use or reconstituted) with very low carbohydrate content, high-quality proteins (milk, whey, pea, soy), and fiber (inulin, FOS). Gluten-free, lactose-free, and vegan options are available. Meal replacements are provided by Therascience or Penta at discounted prices. Participants will self-monitor capillary ketonemia daily, maintain adequate hydration, and avoid intense physical exercise. The Advanced Hybrid Closed Loop (AHCL) insulin delivery system will be used throughout the study with periodic adjustments based on device downloads. At the end of the 4-week intervention, a structured reintroduction of conventional meals will be initiated.

Very Low-Energy Ketogenic Therapy with Advanced Hybrid Closed Loop in Adults with T1D and Obesity

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Diagnosis of type 1 diabetes or autoimmune diabetes for ≥ 12 months
• BMI ≥ 30 kg/m²
• HbA1c \< 9%
• Knowledge and use of carbohydrate counting
• Use of an Advanced Hybrid Closed Loop (AHCL) system for ≥ 3 months and willingness to maintain it during the study
• At least 1 diabetology follow-up visit in the last 12 months (including telemedicine)
• Willingness to purchase meal replacements for the entire study duration

You may not qualify if:

• Ketoacidosis, severe hypoglycemia with seizures/coma, or severe hyperglycemia requiring hospitalization in the last 6 months
• Febrile illness within the last 2 weeks
• Dietary restrictions or intolerances incompatible with study food supplies
• Celiac disease, gastroparesis, food allergies
• Intense physical exercise \>2 hours on \>3 days per week
• History or risk of eating disorder, or other psychiatric disorders
• Recreational drug use or excessive alcohol consumption
• Chronic kidney disease (eGFR \<60 ml/min)
• Gallstones
• Liver failure
• Heart failure (NYHA III-IV), unstable angina, cardiac arrhythmia, myocardial infarction, or stroke within the last 12 months
• Respiratory failure
• Severe or active infections
• Planned elective surgery
• Rare metabolic diseases (porphyria, CPT2 deficiency, mitochondrial fatty acid oxidation defect, pyruvate carboxylase defect)

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari: lead

Study Sites (1)

University Hospital Policlinico Consorziale

Bari, Italy, 70124, Italy

RECRUITING

Related Publications (16)

• Barrea L, Caprio M, Grassi D, Cicero AFG, Bagnato C, Paolini B, Muscogiuri G. A New Nomenclature for the Very Low-Calorie Ketogenic Diet (VLCKD): Very Low-Energy Ketogenic Therapy (VLEKT). Ketodiets and Nutraceuticals Expert Panels: "KetoNut", Italian Society of Nutraceuticals (SINut) and the Italian Association of Dietetics and Clinical Nutrition (ADI). Curr Nutr Rep. 2024 Sep;13(3):552-556. doi: 10.1007/s13668-024-00560-w. Epub 2024 Jul 23.

  PMID: 39039372 BACKGROUND

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  PMID: 25898950 BACKGROUND

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  PMID: 34598919 BACKGROUND

• Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group; Nathan DM, Zinman B, Cleary PA, Backlund JY, Genuth S, Miller R, Orchard TJ. Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005). Arch Intern Med. 2009 Jul 27;169(14):1307-16. doi: 10.1001/archinternmed.2009.193.

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• Weight gain associated with intensive therapy in the diabetes control and complications trial. The DCCT Research Group. Diabetes Care. 1988 Jul-Aug;11(7):567-73. doi: 10.2337/diacare.11.7.567.

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MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Obesity; Weight Loss

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Endocrinology, Director of Department of Precision and Regenerative Medicine and Ionian Area, Chief of Division of Endocrinology - University Hospital Policlinico Consorziale

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: September 22, 2025
• Study Start: January 16, 2025
• Primary Completion: December 14, 2025
• Study Completion: March 1, 2026
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

IT (1)