Clinical trial NCT06503809: Efficacy and Safety of a Ketogenic Diet in Type 1 Diabetes
Official title: Efficacy and Safety of a Ketogenic Diet in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 1
Keywords: Type 1 diabetes
Ketogenic diet
Insulin sensitivity
Continuous glucose monitoring
Hypoglycemia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2024-07-16
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Despite strong evidence that tight control of blood sugar reduces the risk of diabetes complications, most people with type 1 diabetes do not achieve recommended blood sugar targets. This randomized controlled trial will test whether a very-low- carbohydrate ketogenic diet can effectively and safely improve blood sugar control in adults with type 1 diabetes.

Detailed description: A very-low-carbohydrate ketogenic diet (≤50 g carbohydrate/day) could reduce glycemic variability, total daily insulin requirement, and HbA1c in people with type 1 diabetes (T1D). Indeed, several case series and observational studies of using a ketogenic diet (KD) in people with T1D have observed such benefits. However, no randomized controlled trials (RCTs) have evaluated the efficacy of KD for \>7 days in people with T1D. In addition, there are serious concerns regarding the safety and tolerability of a KD in patients with T1D, including the potential for an increased risk of hypoglycemia, diabetic ketoacidosis, dyslipidemia, insulin resistance, decreased bone mineral density, and impaired quality of life. This study is a 12-week RCT to evaluate the clinical efficacy, metabolic function, safety, socio-behavioral impact, acceptability and potential for dissemination of an isocaloric KD compared with an American Diabetes Association-recommended control diet in adults with T1D.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 and ≤65 years
* T1D diagnosed \>1 year prior to screening
* HbA1c 7.0%-9.0%
* Stable insulin delivery method for the past 30 days
* Ability to read all device instructions and insulin pump settings
* eGFR ≥60 mL/min/1.73 m2
* Use of an insulin pump or insulin delivery by multiple daily injections
* Use of personal CGM for at least 12 weeks and willing to change to Dexcom CGM for the duration of the study, if using a different sensor, to reduce variability in glucose values associated with different CGM products
* Use of cellular phone with data capability for wireless connectivity to the CGM system.

Exclusion Criteria:

* Body mass index \<20.0 or \>34.9 kg/m2
* Severe gastroparesis or history of bariatric surgery
* Diabetes-related hospitalization (including for diabetic ketoacidosis or severe hypoglycemia) within 12 months of screening
* Poorly controlled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg)
* Taking diabetes medications, other than insulin (particularly SGLT2 inhibitors, which are associated with an increased risk of euglycemic DKA)
* Structured exercise \>210 minutes per week
* Pregnant, lactating, not using effective birth control if premenopausal, or planning to become pregnant within the 6-month study period
* Unstable weight (\>4% change in the last 2 months)
* Significant organ system dysfunction (e.g., severe pulmonary, renal, hepatic, or cardiovascular disease)
* Anemia (Hgb \<10 g/dL)
* Major psychiatric illness
* Active tobacco use (\>8 cigarettes/day) or illegal drug use
* Regular alcohol consumption (\>10 standard drinks per week)
* Use of medications known to affect the study outcome measures or increase the risk of study procedures that cannot be temporarily discontinued for this study
* Familial hypercholesterolemia
* Active eating disorder
* Dietary restrictions incompatible with a very-low-carbohydrate KD, vegan diet, vegetarian diet, severe lactose intolerance, severe aversion/sensitivity to eggs, fish, nuts, wheat, or soy, and any anaphylactic food allergy
* Already consuming a low-carbohydrate (\<130 g/day) diet
* Persons who are not able to grant voluntary informed consent
* Persons who are unable or unwilling to follow the study protocol or who, for any reason, the research team considers an inappropriate candidate for the study.

Primary outcomes:
measure: Change in continuous glucose monitor (CGM) time-in-range
timeFrame: Before and immediately after the dietary intervention
measure: Change in skeletal muscle insulin sensitivity
timeFrame: Before and immediately after the dietary intervention
Secondary outcomes:
measure: Change in daily insulin requirements
timeFrame: Assessed before, during, and immediately after the dietary intervention
measure: Change in 24-hour glucose concentrations
timeFrame: Before and immediately after the dietary intervention
measure: Change in 24-hour glucagon concentrations
timeFrame: Before and immediately after the dietary intervention
measure: Change in whole-body palmitate turnover
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma lipid profile
timeFrame: Before and immediately after the dietary intervention
measure: Change in hepatic de novo lipogenesis
timeFrame: Before and immediately after the dietary intervention
measure: Change in de novo cholesterol synthesis
timeFrame: Before and immediately after the dietary intervention
measure: Change in fat mass
timeFrame: Before and immediately after the dietary intervention
measure: Change in fat-free mass
timeFrame: Before and immediately after the dietary intervention
measure: Change in intrahepatic triglyceride content
timeFrame: Before and immediately after the dietary intervention
measure: Change in specific adipose tissue volumes
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma hs-CRP
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma PAI-1
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma IL-6
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma TNF-alpha
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma markers of liver function
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma markers of kidney function
timeFrame: Before and immediately after the dietary intervention
measure: Change in plasma markers of bone turnover
timeFrame: Before and immediately after the dietary intervention
measure: Change in percent time in hypoglycemia
timeFrame: Before and immediately after the dietary intervention
measure: Change in percent time in hyperglycemia
timeFrame: Before and immediately after the dietary intervention
measure: Level 3 hypoglycemia event rate
timeFrame: During the dietary intervention
measure: Diabetic ketoacidosis event rate
timeFrame: During the dietary intervention
measure: Change in bone mineral density
timeFrame: Before and immediately after the dietary intervention
measure: Change in sociobehavioral factors
timeFrame: Before and immediately after the dietary intervention
measure: Knowledge and perceptions of the diet
timeFrame: Immediately after the dietary intervention
measure: Adaptations needed to implement the diet at the population level
timeFrame: Immediately after the dietary intervention
measure: Change in glycated hemoglobin and albumin
timeFrame: Before, during, and immediately after the dietary intervention
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Samuel Klein, MD
role: PRINCIPAL_INVESTIGATOR
References: