Clinical trial NCT05681468: Metabolic and Inflammatory Outcomes of the Ketogenic Diet Comparing Saturated and Unsaturated Fat Sources
Official title: Metabolic and Inflammatory Outcomes of the Ketogenic Diet Comparing Saturated and Unsaturated Fat Sources
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: PreDiabetes
Diabetes Mellitus, Type 2
Overweight and Obesity
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2023-01-12
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Controlled Trial (3-parallel arm study).
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to compare a healthy KETO diet supplemented with canola oil (KETO-Can) compared to a traditional KETO diet high in saturated fat (KETO-Sat) and low-fat diet (LFD) in adults at high risk of or diagnosed with type 2 diabetes. The main question\[s\] it aims to answer are:

* Effects on CVD risk factors (plasma cholesterol, TG, ApoB100, glucose, insulin and HbA1C).
* Effects on systemic inflammation and immune function.
* Adherence to interventions.

Participants will be randomized into 1 of the dietary treatments during which they will follow a Keto or a low-fat diet.

Comparisons among groups at 3 and 6 months of intervention will be conducted.

Detailed description: The ketogenic diet (KETO) is popular for weight loss and is gaining interest as a treatment for type 2 diabetes (T2D) because it is believed to help manage blood glucose and weight. However, KETO is often high in saturated fats (SFA), which may increase cholesterol and other cardiovascular (CVD) risk factors, such as inflammatory profile. Substituting a heart-healthy oil for SFA may improve these outcomes.

The purpose of our study is to investigate the health beneficial effects of a healthy KETO diet supplemented with Canola oil, compared to a traditional Keto Diet and low-fat diet in adults at high risk of type 2 diabetes. Participants will be randomized to one of these three diets and will receive nutrition counselling during 6 months.

Each month, participants will receive a 1-month supply of canola oil in the KETO-Can group, butter and coconut oil in the KETO-Sat group and whole grain foods (pasta or brown rice) and oatmeal in the LFD group to ensure compliance to key nutrients.

Fasting blood samples will be taken at baseline, 3 and 6 months. Anthropometric measurements (weight (BW), waist circumference (WC), BMI), blood pressure (BP), systemic inflammation (CRP, IL-6, TNF-α, IL-18), immune function, cardiometabolic risk factors (TG, cholesterol, glucose, insulin and HbA1C) will be determined at each time point.

A total of three 24h-recall questionnaires (2 weekdays and 1 weekend day) will be completed at each time point (baseline, 3 months, 6 months). Once a month (in between study visits) a 24h-recall will be completed before meeting the nutrition expert in order to personalize recommendations according to participants' respective diet groups.

As in any nutritional study, adherence for nutrition study is a key factor and will be measured differently during the intervention. Menu examples will be provided for each group to facilitate adherence. Adherence to the study protocol will be assessed by (1) evaluation of 24-h recall data (14 in total). Participants with 11 out of 14 recalls being within meeting dietary objectives will be considered highly compliant, 6 or less would be low compliance; (2) Ketosis state will be measured at each study visit using ketone strips to assess adherence to both KETO diets; (3) Participants will be asked to report the food consumed each month to determine the level of consumption. Finally, fatty acid composition in plasma (short-term) and red blood cells (RBCs; reflect the past 3 months) will be assessed to confirm adherence between the two keto diets.

Eligibility criteria: Inclusion Criteria:

* Having overweight or obesity and HbA1C ≥ 5.7% at screening

Exclusion Criteria:

* Individuals with specific nutritional habits preventing them from adhering to nutritional recommendations
* Pregnant women
* People on dialysis or recommended to follow a low-protein diet (base on glomerular filtration rate)
* Familial hypercholesterolemia or hypertriglyceridemia
* Transitioning trans-gender
* For safety purposes, other individuals would be excluded if are under unstable health conditions.

Primary outcomes:
measure: Effect of diets on plasma triglycerides levels by comparing groups at 3 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 3 months).
timeFrame: 3 months
measure: Effect of diets on plasma triglycerides levels by comparing groups at 6 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 6 months).
timeFrame: 6 months
measure: Effect of diets on LDL-cholesterol levels by comparing groups at 3 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 3 months).
timeFrame: 3 months
measure: Effect of diets on LDL-cholesterol levels by comparing groups at 6 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 6 months).
timeFrame: 6 months
Secondary outcomes:
measure: Effect of diets on blood glucose levels by comparing groups at 3 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 3 months).
timeFrame: 3 months
measure: Effect of diets on blood glucose levels by comparing groups at 6 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 6 months).
timeFrame: 6 months
measure: Effect of diets on insulin levels by comparing groups at 3 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 3 months).
timeFrame: 3 months
measure: Effect of diets on insulin levels by comparing groups at 6 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 6 months).
timeFrame: 6 months
measure: Effect of diets on hemoglobin A1C (HbA1c) levels by comparing groups at 3 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 3 months).
timeFrame: 3 months
measure: Effect of diets on hemoglobin A1C (HbA1c) levels by comparing groups at 6 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 6 months).
timeFrame: 6 months
measure: Effect of diets on ApoB100 levels by comparing groups at 3 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 3 months).
timeFrame: 3 months
measure: Effect of diets on ApoB100 levels by comparing groups at 6 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 6 months).
timeFrame: 6 months
measure: Effect of diets on immune function and Inflammation measured by blood Immune Markers by comparing groups at 3 months of intervention and changes over time within each group compared to baseline.
timeFrame: 3 months
measure: Effect of diets on immune function and Inflammation measured by blood Immune Markers by comparing groups at 6 months of intervention and changes over time within each group compared to baseline.
timeFrame: 6 months
measure: Effect of diets on inflammatory markers (C-reactive protein (CRP)) by comparing groups at 3 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 3 months).
timeFrame: 3 months
measure: Effect of diets on inflammatory markers (C-reactive protein (CRP)) by comparing groups at 6 months of intervention (i.e. control low fat diet and the 2 keto groups) and changes over time within each group (i.e. baseline vs. 6 months).
timeFrame: 6 months
Other outcomes:
measure: Adherence to diet interventions using 24-hour dietary assessment tool
timeFrame: 4 weeks
measure: Change in fatty acid composition to confirm adherence to the diets at 3 months
timeFrame: 3 months
measure: Change in fatty acid composition to confirm adherence to the diets at 6 months
timeFrame: 6 months
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: Catherine Chan, PhD
role: PRINCIPAL_INVESTIGATOR
References: