Low-Calorie Diet in People With Prediabetes/Metabolic Syndrome

NCT04786418 | Completed

• 1 other identifier: UoL001503
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Significant weight reduction, achieved by low-calorie diet (LCD), will mobilise ectopic fat (visceral and particularly liver fat), improving insulin sensitivity and other metabolic syndrome components, with secondary beneficial effects on cardiac structure and function. This CALIBRATE study (metabolic, multi-organ and effects of low-calorie diet in younger obese patients with pre-diabetes) will compare the effects of a safe and effective 12-month weight management intervention, initially using a low-calorie, liquid replacement diet for 12 weeks, anticipating at least 10% reduction in body weight. The investigators will examine how much the weight loss improves the metabolic abnormalities that precede type 2 diabetes (T2D), and in reversing the pre-clinical/subtle clinical abnormalities of the liver and heart that precede liver and cardiovascular disease (CVD). This study will compare the effects of a safe and effective 12-month weight management intervention, initially using a low-calorie, liquid replacement diet for 12 weeks, followed by a weight maintenance phase. The investigators will examine how much the weight loss improves the metabolic and neuropathic abnormalities that precede and accompany type 2 diabetes (T2D), and in reversing the pre-clinical/subtle clinical abnormalities of the liver and heart that precede liver and cardiovascular disease. In an additional optional sub-study, the investigators will additionally assess how the weight loss impacts upon appetite regulation within the brain with functional MRI (fMRI).

Conditions

Obesity; NAFLD; Fatty Liver; Pre Diabetes; Metabolic Syndrome

Keywords

Obesity; Metabolic Syndrome; Pre Diabetes; NAFLD; Fatty Liver; Low-calorie diet; functional magnetic resonance imaging; skin biopsy; appetite regulation

Outcome Measures

Primary Outcomes (1)

• Changes in liver fat >5 percent, determined by MRI, from baseline to after 12 months of intervention.

  For liver fat, diagnosis of NAFLD is based on a threshold of a value \>5.5 percent. The investigators anticipate having a 45 percent difference in the proportion in whom liver fat percentage reduces by at least 5 percent between the groups (50 percent of LCD will have an absolute reduction in liver fat of 5 percent vs. 5 percent of controls). The investigators chose an absolute reduction of liver fat of 5 percent as this reduction is clinically meaningful.

  Changes will be measured at baseline and at 12 months.

Secondary Outcomes (30)

• Body Mass Index

  Changes will be measured at baseline and at 12 months.

• Body weight

  Changes will be measured at baseline and at 12 months.

• Waist Circumference

  Changes will be measured at baseline and at 12 months.

• Blood pressure

  Changes will be measured at baseline and at 12 months.

• Liver biochemistry: Alanine transaminase

  Changes will be measured at baseline and at 12 months.

Study Arms (2)

Control group

ACTIVE COMPARATOR

Participants will be given standard advice about healthy eating, physical activity and management of weight during the study visit, in line with current NHS practice. There will be a total of 9 study visits for this group.

Other: Standard of care

Low-calorie diet intervention group

EXPERIMENTAL

Participants will received a special diet involving 25 regular visits and intensive management. Participants will be given a supply of especially formulated soups and shakes, a special diet in a form of powder that need to be mixed with 200 ml water.

Dietary Supplement: Low-calorie diet

Interventions

Standard of care OTHER

Participants allocated to the control group will be given standard clinical information regarding healthy eating, physical activity and management of weight, in line with current NHS practise.

Control group

Low-calorie diet DIETARY_SUPPLEMENT

The LCD intervention group, will received a well validated, commercially available, intensive weight management protocol Counterweight-Plus.

Low-calorie diet intervention group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The investigators shall recruit participants with the following characteristics:
• Men and women
• aged 18-55 years\*,
• BMI 30-40 kg/m2 , BMI\>27 kg/m2 for Chinese/South Asians
• Any one of the following three metabolic criteria:
• a diagnosis of prediabetes (HbA1c 42-47 mmol/mol), OR
• NAFLD (based on fatty liver index, FLI \>60). FLI will be determined using waist circumference, BMI, serum triglyceride and GGT (gamma-glutamyltransferase). OR
• a diagnosis of metabolic syndrome using the IDF metabolic syndrome criteria (see below,

You may not qualify if:

• Individuals with normal glucose tolerance (NGT) or type 1 or type 2 diabetes (T2D).
• Anyone engaged in active weight loss (\>5kg weight loss in the last 6 months), currently engaged with weight management service, previous bariatric surgery, on weight-lowering medications (e.g. orlistat or liraglutide) or with a history of an eating disorder.
• planning pregnancy/6 months post-partum,
• known structural cardiac disease or anyone with major atherosclerotic disease
• history of stroke within the last 3 months
• Active mental health illness (e.g. severe depression, bipolar disorder, schizophrenia or other psychotic disorders). Use of drug with known major effects on bodyweight (e.g. corticosteroid, anti-psychotic, anticonvulsants etc).
• Planning pregnancy within the next 6 months and until \>6 months post-partum or breastfeeding
• Substance abuse e.g. drugs/alcohol.
• Eating disorder, previous bariatric surgery, currently taking weight loss drugs or already engaged with weight management service
• Learning difficulties
• A contraindication to magnetic resonance scanning will exclude the patient from the MRI component of the study

Sponsors & Collaborators

• University of Liverpool: lead
• University of Surrey: collaborator
• Perspectum: collaborator

Study Sites (1)

Liverpool University Hospital NHS Foundation Trust are an NHS organisation

Liverpool, L97AL, United Kingdom

Location

Related Publications (1)

• Leslie WS, Ford I, Sattar N, Hollingsworth KG, Adamson A, Sniehotta FF, McCombie L, Brosnahan N, Ross H, Mathers JC, Peters C, Thom G, Barnes A, Kean S, McIlvenna Y, Rodrigues A, Rehackova L, Zhyzhneuskaya S, Taylor R, Lean ME. The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial. BMC Fam Pract. 2016 Feb 16;17:20. doi: 10.1186/s12875-016-0406-2.

  PMID: 26879684 BACKGROUND

MeSH Terms

Conditions

Obesity; Non-alcoholic Fatty Liver Disease; Fatty Liver; Glucose Intolerance; Metabolic Syndrome

Interventions

Standard of Care; Caloric Restriction

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Daniel Cuthbertson

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: There are two study groups: Control groups and low-calorie diet intervention group running alongside.

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: March 8, 2021
• Study Start: June 1, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)