ACT1ON Phase 2 (SMART Pilot) and Phase 3 (Efficacy Trial Development) (ACT1ON DP3)

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

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.

Study Overview

• Status: Completed
• 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

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 Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypocaloric, low carbohydrate; 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; 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.; Other Names: Low carbohydrate diet
Experimental: Hypocaloric, moderate low fat; 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; 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.; Other Names: Low fat diet
Experimental: Mediterranean, 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.	Behavioral: Mediterranean diet, no caloric restriction; 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.; 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

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Elizabeth Mayer-Davis, PhD, UNC Chapel Hill; Principal Investigator: David M Maahs, MD, PhD, Stanford University; Principal Investigator: Richard Pratley, MD, Florida Hospital, Translational Research Institute

Publications and helpful links

General Publications

• Igudesman D, Crandell J, Corbin KD, Muntis F, Zaharieva DP, Casu A, Thomas JM, Bulik CM, Carroll IM, Pence BW, Pratley RE, Kosorok MR, Maahs DM, Mayer-Davis EJ. The Intestinal Microbiota and Short-Chain Fatty Acids in Association with Advanced Metrics of Glycemia and Adiposity Among Young Adults with Type 1 Diabetes and Overweight or Obesity. Curr Dev Nutr. 2022 Oct 30;6(10):nzac107. doi: 10.1093/cdn/nzac107. eCollection 2022 Nov.
• Corbin KD, Igudesman D, Addala A, Casu A, Crandell J, Kosorok MR, Maahs DM, Pokaprakarn T, Pratley RE, Souris KJ, Thomas JM, Zaharieva DP, Mayer-Davis EJ; ACT1ON Consortium. Design of the Advancing Care for Type 1 Diabetes and Obesity Network energy metabolism and sequential multiple assignment randomized trial nutrition pilot studies: An integrated approach to develop weight management solutions for individuals with type 1 diabetes. Contemp Clin Trials. 2022 Jun;117:106765. doi: 10.1016/j.cct.2022.106765. Epub 2022 Apr 20.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2018
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: August 27, 2018
• First Submitted That Met QC Criteria: August 27, 2018
• First Posted (Actual): August 29, 2018

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: March 3, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: overweight; Type 1 diabetes; T1D; weight management; obese; Type 1 diabetes mellitus (T1DM)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 1; Overweight
• Other Study ID Numbers: 18-1025; 1DP3DK113358-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No