Clinical trial NCT05372445: Microbiome and Health Indicators in People With Obesity, Prediabetes and Type 2 Diabetes Undergoing a Lifestyle Intervention
Official title: MicrobiAr: Characterization and Follow-up of Microbiome and Health Indicators in Obese, Pre-Diabetes and Type 2 Diabetes Cohorts Undergoing a Plant-based Diet and Lifestyle Intervention
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Obesity
PreDiabetes
Keywords: microbiota
microbiome
plant-based diet
type 2 diabetes remission
metabolic syndrome
caloric restriction
metabolic pathways
Lead sponsor: National Council of Scientific and Technical Research, Argentina
Sponsor class: OTHER_GOV
Collaborators: name: Facultad de Ingeniería - Universidad Austral
name: Instituto de Inmunología, Genética y Metabolismo (INIGEM, CONICET-UBA)
name: Illumina, Inc.
name: Zymo Research
name: Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática (IBB, CONICET-UNER)
First posted: 2022-05-12
Enrollment: 480
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The incidence of type 2 diabetes worldwide is growing rapidly, being one of the fastest growing global health emergencies of the 21st century according to the International Diabetes Federation. In MicrobiAr the investigators seek to achieve type 2 diabetes remission through a plant-based diet and lifestyle intervention identifying and characterizing key changes on the gut microbiome during clinical transitions. Specifically, the investigators aim to characterize and follow-up metabolic pathways from gut microbiome and how they evolve as long as health indicators do over the 2 years of this study.

Detailed description: The present study has 2 stages, one cross-sectional and the other longitudinal. In the cross-sectional stage, a characterization of a single sampling of 480 people divided into 4 cohorts of 120 people each will be carried out: reference controls, subjects with obesity, with prediabetes and with type 2 diabetes. A clinical history will be made, as long as a 7-day food record and clinical laboratory tests. Anthropometric assessment will be carried out by recording weight, height, waist and hip circumference, determination of waist/hip ratios, as well as taking 4 skinfolds, bicipital, triceps, subscapular and suprailiac, arm and calf measurements and force through a dynamometer. The 480 people will also undergo gut microbiota and microbiome tests from stool samples.

During the longitudinal stage, subjects of each cohort (120 with obesity, 120 with prediabetes and 120 with type 2 diabetes) will be randomly divided into two intervention groups (with 60 subjects each). One group will follow a non-intensive intervention (personalized face-to-face follow-up every 2 months). The other group will follow an intensive intervention (personalized face-to-face follow-up every 3 weeks and a weekly remote group meeting). In both cases, a food plan will be followed based on the recommendations of the nutrition service of the Hospital de Clínicas, Argentina, in accordance with recommendations from the American Diabetes Association (ADA) 2019 guidelines with an emphasis on plant-based diet and whole foods.

Follow-up and nutritional guidance

Groups of 15 subjects from each intervention arm will be led by 3 healthcare professionals. In every case, the group's functions will be:

1. Obtain a unique 7 day food-recall from all subjects, and upload the data to "MAR24" platform (for the transversal stage).
2. Obtain a 2 day food-recall (including one day from the weekend) from all subjects every two months, and upload the data to "MAR24" platform (for the longitudinal stage).
3. Complete a shared spreadsheet with clinical, biochemical and anthropometric parameters of every subject's visits to the hospital.
4. Collaborate in Whatsapp unidirectional groups. In the non-intensive arm, the messages will only be to remember patients about their visits to the hospital, while in the intensive arm it will also be about other activities, such as workshops.
5. Detect subjects who miss their appointments, to establish personalized contact and apply motivational strategies in order to reduce dropout risk.

To accomplish the mentioned tasks, the group leaders will have support from several students from nutrition careers and healthcare professionals.

Influence of physical activity and exercise

A structured physical exercise protocol will be delivered to all subjects. This protocol includes a warm-up, 3 series of 1 minute of eight different strength exercises, with 2 a minute rest. The objective is to accomplish three sessions per week, which can be done in person and supervised by specialists in the Hospital, or online via video call. Subjects will have to record the amount of achieved repetitions in each series of every exercise already done by each session.

The training volume will be adapted according to the subject's capabilities and progress, with the objective of increasing the number of series and reducing resting time between exercises.

Specific follow-up and support proposals for the intensive intervention

In addition to the already mentioned tasks in the follow-up and nutritional guidance's section, for the intensive intervention subjects, group's functions will also be:

1. Collaborate in the assembly and execution of virtual food education workshops;
2. Coordinate weekly meetings with the 15 assigned subjects, where adherence should be encouraged during the first 3 months. Then, meetings will be spaced out at a minimum of 15 days to 30 days;
3. Contribute to the planning of various activities that seek to maximize adherence to the clinical trial of the entire intensive intervention group;
4. Coordinate face-to-face visits for nutritional support every 3 weeks for each subject;
5. Monitoring adherence through 48-hour records (1 day a week and 1 day a weekend) using the MAR24 platform. Data will be collected by phone calls or video calls to each subject with a frequency of 1 call per month.

Eligibility criteria: Inclusion Criteria for control or reference group:

* Subjects without type 2 diabetes, obesity, prediabetes (glucose intolerance), or metabolic syndrome
* HbA1c less than 42mmol/mol (\<5.7%)
* BMI between 18.5 and 24.9

Inclusion Criteria for people with obesity:

* BMI greater than 30

Inclusion Criteria for people with prediabetes:

* Fasting glucose between 110 and 125 mg/dl
* HbA1c between 42 and 47 mmol/mol (5.7% to 6.4%)
* BMI greater than 30

Inclusion Criteria for people with type 2 diabetes:

* Fasting glucose \> 126 mg/dl
* HbA1c \> 48mmol/mol (6.5% or higher)
* BMI greater than 30
* Treatment with metformin at therapeutic dose (1500-2000 mg/day) or maximum tolerated dose.

Exclusion Criteria:

* Subjects with obesity, pre-diabetes medicated with metformin or another drug for diabetes or obesity
* Subjects with type 2 diabetes medicated with another drug that is not metformin
* Subjects with type 2 diabetes diagnosed over 6 years
* Subjects with type 2 diabetes requiring insulin
* Chronic kidney disease grade greater than 3 (measured by EPI)
* Subjects with type 1 diabetes
* Intestinal diseases, Crohn's, ulcerative colitis, celiac disease
* Use of antibiotics in the last 3 months
* Pregnancy, lactation
* Psychiatric disorders
* Eating disorder
* Gastric bypass surgery
* Transplanted people
* Oncological pathology diagnosed less than 5 years
* Subjects who do not wish to sign the informed consent
* Subjects who do not agree to participate in the study over the 2 years follow-up
* Subjects who do not have electronic devices and the internet to hold virtual meetings

Primary outcomes:
measure: Clinical improvements in people with type 2 diabetes, prediabetes, or obesity
timeFrame: at 2 years, checked every 6 months
measure: Gut microbiota metabolic pathways changes
timeFrame: at 2 years, checked every 6 months
Secondary outcomes:
measure: Metabolic syndrome regression
timeFrame: at 2 years, checked every 6 months
measure: Insulin resistance
timeFrame: at 2 years
measure: Gut microbiota diversity changes
timeFrame: at 2 years, checked every 6 months
Other outcomes:
Locations:
city: Capital Federal
country: Argentina
facility: Hospital de Clínicas "José de San Martín"
state: Buenos Aires
Study officials:
affiliation: CONICET Researcher
name: Juan Bustamante, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CONICET Researcher
name: Gustavo Frechtel, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5. doi: 10.1161/CIRCULATIONAHA.109.192644. Epub 2009 Oct 5.
citation: Riddle MC, Cefalu WT, Evans PH, Gerstein HC, Nauck MA, Oh WK, Rothberg AE, le Roux CW, Rubino F, Schauer P, Taylor R, Twenefour D. Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes. Diabetes Care. 2021 Aug 30;44(10):2438-44. doi: 10.2337/dci21-0034. Online ahead of print.