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

Not Applicable

Completed

• Conditions: Diabetes Mellitus, Type 1; Overweight and Obesity
• Interventions: Behavioral: Hypocaloric, moderate low fat diet; Behavioral: Mediterranean diet, no caloric restriction; Behavioral: Hypocaloric, low carbohydrate diet

• Registration Number: NCT03651622
• Lead Sponsor: University of North Carolina, Chapel Hill

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.

Study Timeline

• Study First Submitted: 2018-08-27
• Study First Submitted QC: 2018-08-27
• Study First Posted: 2018-08-29
• Study Start: 2018-11-12
• Primary Completion: 2021-03-31
• Study Completion: 2021-03-31
• Status Verified: 2021-04
• Results First Submitted: 2022-01-27
• Results First Submitted QC: 2022-03-03
• Last Update Submitted: 2022-03-03
• Results First Posted: 2022-03-04
• Last Update Posted: 2022-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 68

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Hypocaloric, moderate low fat	Hypocaloric, moderate low fat diet	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.
Mediterranean, no caloric restriction	Mediterranean diet, no caloric restriction	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.
Hypocaloric, low carbohydrate	Hypocaloric, low carbohydrate diet	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.

Primary Outcome Measures

Name	Time	Method
Change in Weight - Randomization 2	3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit	Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.
Change in Weight - Randomization 3	6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit	Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.
Change in HbA1C - Randomization 1	Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit	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.
Change in HbA1C - Randomization 3	6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit	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.
Change in Time in Clinical Hypoglycemia - Randomization 2	2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit	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.
Change in Weight - Randomization 1	Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit	Weight in kilograms will be obtained at measurement visits at the beginning and end of this three-and-a-half month time period.
Change in Time in Clinical Hypoglycemia - Randomization 1	2 weeks of wear from Baseline Visit (-14 Days), 2 weeks of wear from 3 Month (Measurement 2) Visit	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.
Change in HbA1C - Randomization 2	3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit	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.
Change in Time in Clinical Hypoglycemia - Randomization 3	2 weeks of wear from 6.5 Month (Measurement 3) Visit, 2 weeks of wear from 10 Month (Measurement 4) Visit	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.

Secondary Outcome Measures

Name	Time	Method
Change in Body Fat - Randomization 1	Baseline (-14 Days prior to Randomization 1 Visit), 3 Month (Measurement 2) Visit	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.
Change in Body Fat - Randomization 2	3 Month (Measurement 2) Visit, 6.5 Month (Measurement 3) Visit	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.
Change in Time in Target Glucose Range - Randomization 2	2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit	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.
Change in Time in Target Glucose Range - Randomization 3	2 weeks of wear from 6.5 Month (Measurement 3) Visit, 2 weeks of wear from 10 Month (Measurement 4) Visit	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.
Change in Body Fat - Randomization 3	6.5 Month (Measurement 3) Visit, 10 Month (Measurement 4) Visit	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.
Change in Time in Target Glucose Range - Randomization 1	2 weeks of wear from 3 Month (Measurement 2) Visit, 2 weeks of wear from 6.5 Month (Measurement 3) Visit	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.

Trial Locations

Locations (2)

Stanford University; 🇺🇸 Palo Alto, California, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States