ACT1ON Phase 2 (SMART Pilot) and Phase 3 (Efficacy Trial Development)

Study Overview
=================
Brief Summary
-----------------
An initial pilot and feasibility study will be conducted using a Sequential, Multiple Assignment, Randomized Trial (SMART) design to identify acceptable and effective dietary strategies to optimize both glycemic control and weight management in young adults with Type 1 diabetes (T1D). This pilot trial will include a ten-and-a-half month behavioral intervention, with co-primary outcomes of glycemic control (HbA1C and hypoglycemia) and weight loss. The pilot trial will assess acceptability and adherence to three distinct, evidence-based dietary approaches designed to address weight management and glycemic control. Behavioral counseling strategies, use of carbohydrate counting for insulin dosing, and encouragement of physical activity will be the same across the three dietary approaches. COVID-19 PROVISIONS: Due to restrictions in place on in-person visits due to COVID-19 precautions, some subjects may remain in the study longer than 10.5 months. As of June 2020, the study transitioned to a completely virtual format. Those who were due for a measurement visit during the time that research activities were halted, prior to the approval of the virtual procedures, remained on the diet they were currently assigned to, supported by bi-weekly Registered Dietitian (RD) counseling, until they were able to be scheduled for a virtual visit.

Detailed Description
-----------------
Eight-four participants will be randomized in total; 42 at the University of North Carolina (UNC), 42 at Stanford. COVID-19 Provisions: Due to impacts of COVID-19, the study was forced to cease recruitment early. 40 subjects were randomized at UNC and 29 were randomized at Stanford, for a total of 69 subjects across sites. Procedures (methods): Three distinct dietary approaches will be tested. Dietary approaches are as follows: Diet 1: hypocaloric, moderate low fat (30% calories from fat) weight management based on the Look AHEAD study Diet 2: hypocaloric, low carbohydrate (15-20% calories from carbohydrate, 59-63% as total fat (<10% saturated fat, at least 37% monounsaturated fat, remaining as polyunsaturated fat) Diet 3: advice to select a healthy Mediterranean dietary pattern with no caloric restriction Participants will complete measurement visits at baseline (-14 days), 3 mos, 6.5 mos, and 10 mos. All visits transitioned to a virtual format as of 6/2020 due to COVID-19 provisions. Participants will complete a total of 23 intervention sessions over an approximately 10-and-a-half month period (Eight longer sessions (teleconference) and 15 telephone check-ins) Participants will be randomized to one of the three diets for a minimum of a three-and-a-half month period. Re-randomization is possible following the 3 month and/or 6.5 month measurement visits. Re-randomization is based on acceptability of diet (self-report), non-severe hypoglycemic events (self-report), and not achieving significant weight change (defined as losing at least 2% of body weight from previous study visit), and worsening glycemic control (increase in Hemoglobin A1c of >/= 0.5% from previous study visit). Re-randomization will occur after the 14-day continuous glucose monitoring (CGM) wear period that will be initiated at each measurement visit.

Official Title
-----------------
Accelerating Solutions to Optimize Glycemic Control and Weight Management In Young Adults With Type 1 Diabetes

Conditions
-----------------
Diabetes Mellitus, Type 1, Overweight and Obesity

Intervention / Treatment
-----------------
* Behavioral: Hypocaloric, low carbohydrate diet
* Behavioral: Hypocaloric, moderate low fat diet
* Behavioral: Mediterranean diet, no caloric restriction


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Individuals 19-30 years old at enrollment History of Type 1 diabetes for greater than one year Latest hemoglobin A1c less than 13% BMI of 27-39 Exclusion Criteria: Individuals with other metabolic disorders, unstable thyroid disease, diagnosed eating disorder, prohibitive strict dietary restrictions or those with other serious condition that renders participation inappropriate Individuals who have experience diabetic ketoacidosis (DKA) or severe hypoglycemia requiring outside assistance in the last 6 months Females who are pregnant, breastfeeding, have delivered a baby in the last 12 months, or are planning to become pregnant during the study period. Individuals unwilling to follow any of the three study diets Individuals who monitor blood glucose less than 3 times a day

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This initial pilot and feasibility study uses a Sequential, Multiple Assignment, Randomized Trial (SMART) design to identify acceptable and effective dietary strategies to optimize both glycemic control and weight management. The study will be done at UNC and Stanford. Sequential randomization will occur at 0, 3.5, and 7 months. Following the baseline measurement visit and two week run-in period, participants will be randomized to one of three diets (stratified by site with block size of 4). Using a priori decision rules at 3.5 and 7 months post-initial randomization, those for whom the assigned diet is not acceptable or effective will be re-randomized (or re-assigned if only one diet remains untried). 10.5 months of follow-up time allows for evaluation of the effect of diets on initial weight loss and on early maintenance of initial weight loss. Decision criteria for re-randomization will incorporate clinical outcomes (glycemic control and weight change) and acceptability of the diet.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypocaloric, low carbohydrate<br>Behavioral intervention to include lifestyle counseling on hypocaloric, low carbohydrate diet (15-20% calories from carbohydrate, 59-63% as total fat (<10% saturated fat, at least 37% monounsaturated fat, remaining as polyunsaturated fat). Using a priori decision rules at 3.5 and 7 months post-initial randomization, those for whom the diet assigned is not acceptable or is not effective will be re-randomized. | Behavioral: Hypocaloric, low carbohydrate diet<br>* Participants will be advised on use of a hypocaloric, low carbohydrate diet using lifestyle counseling to include motivational interviewing and problem solving skills training strategies.<br>* Other names: Low carbohydrate diet;|
| Experimental: Hypocaloric, moderate low fat<br>Behavioral intervention to include lifestyle counseling on hypocaloric, moderate low fat diet (30% calories from fat) weight management based on the Look AHEAD study. Using a priori decision rules at 3.5 and 7 months post-initial randomization, those for whom the diet assigned is not acceptable or is not effective will be re-randomized. | Behavioral: Hypocaloric, moderate low fat diet<br>* Participants will be advised on use of a hypocaloric, moderate low fat diet using lifestyle counseling to include motivational interviewing and problem solving skills training strategies.<br>* Other names: Low fat diet;|
| Experimental: Mediterranean, no caloric restriction<br>Behavioral intervention to include lifestyle counseling on selecting a healthy Mediterranean diet, no caloric restriction. Using a priori decision rules at 3.5 and 7 months post-initial randomization, those for whom the diet assigned is not acceptable or is not effective will be re-randomized. | Behavioral: Mediterranean diet, no caloric restriction<br>* Participants will be advised on use of a healthy Mediterranean-based eating plan using lifestyle counseling to include motivational interviewing and problem solving skills training strategies.<br>* Other names: Mediterranean diet;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight - Randomization 1 | Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period. | Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit | 
| Change in Weight - Randomization 2 | Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period. | 3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit | 
| Change in Weight - Randomization 3 | Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period. | 6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit | 
| Change in HbA1C - Randomization 1 | HbA1c will be measured from a blood sample collected from participants. Blood will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period. | Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit | 
| Change in HbA1C - Randomization 2 | HbA1c will be measured from a blood sample collected from participants. Blood will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period. | 3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit | 
| Change in HbA1C - Randomization 3 | HbA1c will be measured from a blood sample collected from participants. Blood will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period. | 6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit | 
| Change in Time in Clinical Hypoglycemia - Randomization 1 | Change in the percent of time spent in clinical hypoglycemia (54-69 mg/dl) during Continuous Glucose Monitor (CGM) wear time will be assessed between the two weeks of wear from CGM insertion at Baseline Visit (-14 days) and the two weeks of wear from the insertion of the CGM at Measurement Visit 2. | 2 weeks of wear from Baseline Visit (-14 Days), 2 weeks of wear from 3 Month (Measurement 2) Visit | 
| Change in Time in Clinical Hypoglycemia - Randomization 2 | Change in the percent of time spent in clinical hypoglycemia (54-69 mg/dl) during CGM wear time will be assessed between the two weeks of wear from CGM insertion at Measurement 2 Visit and from CGM insertion at Measurement 3 Visit. | 2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit | 
| Change in Time in Clinical Hypoglycemia - Randomization 3 | Change in the percent of time spent in clinical hypoglycemia (54-69 mg/dl) during CGM wear time will be assessed between the two weeks of wear from CGM insertion at Measurement 3 Visit and from CGM insertion at Measurement 4 Visit. | 2 weeks of wear from 6.5 Month (Measurement 3) Visit, 2 weeks of wear from 10 Month (Measurement 4) Visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Fat - Randomization 1 | Percent fat mass and percent fat free mass were measured via a dual-energy x-ray absorptiometry (DXA) scan at the beginning and end of this time three-and-a-half-month time period. COVID-19 PROVISIONS: Due to precautions required to prevent the spread of COVID-19, all in-person visits were discontinued as of 3/25/2020. As of this date, DXA scans at both sites were discontinued. Analysis on existing data continued, but no new DXA data were collected. | Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit | 
| Change in Body Fat - Randomization 2 | Percent fat mass and percent fat free mass were measured via a dual-energy x-ray absorptiometry (DXA) scan at the beginning and end of this time three-and-a-half-month time period. COVID-19 PROVISIONS: Due to precautions required to prevent the spread of COVID-19, all in-person visits were discontinued as of 3/25/2020. As of this date, DXA scans at both sites were discontinued. Analysis on existing data continued, but no new DXA data were collected. | 3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit | 
| Change in Body Fat - Randomization 3 | Percent fat mass and percent fat free mass were measured via a dual-energy x-ray absorptiometry (DXA) scan at the beginning and end of this time three-and-a-half-month time period. COVID-19 PROVISIONS: Due to precautions required to prevent the spread of COVID-19, all in-person visits were discontinued as of 3/25/2020. As of this date, DXA scans at both sites were discontinued. Analysis on existing data continued, but no new DXA data were collected. | 6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit | 
| Change in Time in Target Glucose Range - Randomization 1 | Change in percent of time spent in a pre-defined range of relative euglycemia (70-180 mg/dl, for a person with Type 1 diabetes) during CGM wear time, will be assessed between the two weeks of wear from CGM insertion at Baseline Visit (-14 days) and the two weeks of wear from CGM insertion at Measurement Visit 2. | 2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit | 
| Change in Time in Target Glucose Range - Randomization 2 | Change in percent of time spent in a pre-defined range of relative euglycemia (70-180 mg/dl, for a person with Type 1 diabetes) during CGM wear time, will be assessed between the two weeks of wear from CGM insertion at Measurement 2 Visit and from CGM insertion at Measurement 3 Visit. | 2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit | 
| Change in Time in Target Glucose Range - Randomization 3 | Change in percent of time spent in a pre-defined range of relative euglycemia (70-180 mg/dl, for a person with Type 1 diabetes) during CGM wear time, will be assessed between the two weeks of wear from CGM insertion at Measurement 3 Visit and from CGM insertion at Measurement 4 Visit. | 2 weeks of wear from 6.5 Month (Measurement 3) Visit, 2 weeks of wear from 10 Month (Measurement 4) Visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 1 diabetes, T1D, Type 1 diabetes mellitus (T1DM), weight management, overweight, obese