Low Energy Diet and Familial Partial Lipodystrophy

Evaluating the Therapeutic Efficacy and Metabolic Impact of a Low Energy Diet (LED) in People With Familial Partial Lipodystrophy and Diabetes

To evaluate the therapeutic efficacy and metabolic impact of a low energy diet (LED) in people with familial partial lipodystrophy and diabetes. Participants will be provided with a LED (total diet replacement) for 12 weeks, before the introduction of a stepped food transition. Metabolic effects will continue to be assessed for 1 year. In order to better understand why this intervention changes insulin sensitivity, we will also collect adipose and muscle tissue samples at baseline and 12 weeks into the intervention in participants willing to have these procedures performed. These samples will be used for histological, metabolite, gene expression and protein expression analyses.

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Diet Modification; Lipodystrophy
• Intervention / Treatment: Dietary supplement: Total Dietary Replacement

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mandour O Mandour; Phone Number: 01223768625; Email: mom30@cam.ac.uk

Study Locations

• United Kingdom
  • Cambridge, United Kingdom
    • Recruiting
    • Cambridge University Hospital NHS Foundation Trust
    • Principal Investigator: David Savage
    • Contact: Mandour O Mandour, MBBS, MRCP; Phone Number: +441233768455; Email: mom30@cam.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Familial Partial Lipodystrophy
• Age >= 18 yrs
• T2DM
• Willingness to check daily blood sugars
• HbA1c between 53mmol(7%)- 108 mmol(12%)
• Weight stable for 3 months
• Capacity to consent

Exclusion Criteria:

• Pregnancy
• Untreated thyroid dysfunction (patients who have been euthyroid on medication for at least 3 months can be included)
• Use of medication adversely that affects diabetes control (e.g. steroids/ immunosuppressants/ certain antipsychotics)
• Incapacity to give informed consent
• History of an eating disorder/ purging behaviour
• Previous gastric bypass/ banding
• Use of Leptin Therapy
• Untreated retinopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm Study; Total Diet Replacement for 12 weeks, food reintroduction 6 weeks	Dietary supplement: Total Dietary Replacement; Total Dietary Replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A change from baseline in HbA1c	mmol/mol	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A change from baseline in HbA1c	mmol/mol	1 year
A change from baseline in fasting glucose	mmol/l	12 weeks, 1 year
A change from baseline in triglycerides	mmol/l	12 weeks, 1 year
A change from baseline in liver fat	% liver fat on MRI	12 weeks, 1 year
A change from baseline in pancreatic fat	% pancreatic fat on MRI	12 weeks, 1 year
A change from baseline in insulin sensitivity	Insulin pmol/l values during oral glucose tolerance test	12 weeks, 1 year
A change from baseline in quality of life scores	Change in scores of EQ-5D-3L Quality of Life measurement from baseline. EQ-5D-3L is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life. It comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results into a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.	12 weeks, 1 year
A change from baseline in anxiety scores	Change in scores of Generalised Anxiety Disorder-7 (GAD 7) from baseline. Change in scores of Generalised Anxiety Disorder-7 (GAD 7) from baseline. The Generalised Anxiety Disorder-7 (GAD 7) Questionnaire is a 7 item measurement that is used to measure or assess the severity of generalised anxiety disorder (GAD) The index scores are as follows: 0 - 4 No Anxiety 5 - 10 Mild Anxiety 11 - 15 Moderate Anxiety 15 - 21 Severe Anxiety	12 weeks, 1 year
A change from baseline in depression scores	Change in scores of Patient Health Questionnaire-9 (PHQ9), from baseline. The PHQ-9 is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. The responses for each of the 9 items are: 0 - Not at all; 1 - Several days; 2 - More than half the day; 3 - Nearly every day The score ranges are: 0 - 4 None 5 - 9 Mild 10 - 14 Moderate 15 - 19 Moderately Severe 20 - 27 Severe	12 weeks, 1 year
A change from baseline in antidiabetic medication use	A change in the amount of antidiabetic drugs taken and/or a change in dose.	12 weeks, 1 year
Adult Eating Behaviour Questionnaire	Change in scores in eating behaviour	12 weeks, 1 year
The Three Factor Eating Questionnaire	Change in scores in The Three Factor Eating Questionnaire	12 weeks, 1 year

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: David Savage, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge

Publications and helpful links

General Publications

• Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 2018 Feb 10;391(10120):541-551. doi: 10.1016/S0140-6736(17)33102-1. Epub 2017 Dec 5.
• Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011 Oct;54(10):2506-14. doi: 10.1007/s00125-011-2204-7. Epub 2011 Jun 9.

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: March 26, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; Diet; Familial Partial Lipodystrophy; FPLD; Total Diet Replacement
• Additional Relevant MeSH Terms: Laminopathies; Genetic Diseases, Inborn; Metabolic Diseases; Skin Diseases; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Skin Diseases, Metabolic; Lipodystrophy; Lipodystrophy, Familial Partial
• Other Study ID Numbers: A095183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No