Low Energy Diet and Familial Partial Lipodystrophy

Study Overview
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Brief Summary
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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.

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

Conditions
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Lipodystrophy, Diabetes, Diet Modification

Intervention / Treatment
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* Dietary Supplement: Total Dietary Replacement


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm Study<br>Total Diet Replacement for 12 weeks, food reintroduction 6 weeks | Dietary Supplement: Total Dietary Replacement<br>* Total Dietary Replacement<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FPLD, Familial Partial Lipodystrophy, Diet, Total Diet Replacement, Diabetes