Clinical trial NCT03421301: Dietary Intervention Modifies Gut Microbiota in Type 2 Diabetes.
Official title: A Dietary Intervention With Functional Foods Reduce Metabolic Endotoxemia and Attenuates Biochemical Abnormalities in Subjects With Type 2 Diabetes by Modifying the Gut Microbiota.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Keywords: gut microbiota
functional foods
branched chain amino acids
TMAO
type 2 diabetes
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
Collaborators: name: University of Connecticut
First posted: 2018-02-05
Enrollment: 81
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In the first stage, the participants with type 2 diabetes consumed a reduced-energy diet tailored to provide a 500-kcal/d deficit as recommended by NIH (8) the with respect to their habitual diet for 15 days. In the second stage the participants continued to consume the reduced energy diet with the addition of a combination of functional foods (dietary portfolio; DP). The DP provided 200 kcal that were subtracted from the diet. The DP consisted of a mi The kcal, appearance and flavor were similar in DP and P. The DP and P was given in a package in dehydrated form ready to be dissolved in water. The DP was divided into two packages, the first package contained 17.3 g of DP or P given in the breakfast and dissolved in 250 ml and the second package was given at the dinner time (15:00-16:00 h) and contained 34.7g of P and DP dissolved in 300 mL of water.
Primary purpose: TREATMENT

Brief summary: Aim: To study the effect of a dietary intervention with functional foods on gut microbiota in subjects with type 2 diabetes Materials and methods: Patients with type 2 diabetes were enrolled in a double-blind, parallel-arm, placebo-control study were randomized to receive a dietary portfolio (DP) or placebo (P) treatment for 3 mo. The primary endpoint was the effect of a dietary portfolio based on functional foods on gut microbiota. Secondary endpoints were biochemical parameters, branched chain amino acids, TMAO

Detailed description: This study was a single-center, randomized, controlled, double-blind, parallel versus placebo that consisted of six visits. The first visit was a screening evaluation to determine whether subjects meet the inclusion criteria. The selected subjects were invited to a second visit that consisted of a medical history, 2-h oral glucose tolerance test (OGTT), collection of stool samples for DNA isolation and collection of 5 ml blood sample. The participants received the first stage dietary strategy for 15 days. In the third visit and second stage of dietary treatment, subjects were randomized to received the dietary portfolio (DP) or placebo (P) treatment accompanied of the reduced energy diet for 1 mo. In the fourth and fifth visits, with a 1 mo interval, dietary assessment and compliance to the DP or P was evaluated. During each follow-up visit, a 24-h dietary recall was collected, a physical activity questionnaire was filled out and anthropometric and clinical parameters were assessed. In the sixth visit, a 2-h oral glucose tolerance test (OGTT) was performed, and a stool sample for DNA isolation and 5 ml blood were collected.

Dietary Intervention In the first stage, the participants consumed a reduced-energy diet tailored to provide a 500-kcal/d deficit as recommended by NIH (8) the with respect to their habitual diet for 15 days. The diet plan consisted in 45-55% carbohydrates, 15-20% protein, 25-35% fat, \<7% saturated fat, 200 mg/d cholesterol, 20-35g fiber, 2000-3000 mg/d sodium based on total energy. In the second stage the participants continued to consume the reduced energy diet with the addition of a combination of functional foods (dietary portfolio; DP). The DP provided 200 kcal that were subtracted from the diet. The DP consisted of a mixture of 14g of dehydrated nopal, 4g of chia seed, 30g of soy protein, 4g of inulin,) and 1g of flavoring. The placebo (P) consisted of 28 g of calcium caseinate, 15g of maltodextrin and 1g of flavoring. The kcal, appearance and flavor were similar in DP and P. The DP and P was given in a package in dehydrated form ready to be dissolved in water. The DP was divided into two packages, the first package contained 17.3 g of DP or P given in the breakfast and dissolved in 250 ml and the second package was given at the dinner time (15:00-16:00 h) and contained 34.7g of P and DP dissolved in 300 mL of water.

Dietary compliance Dietary compliance was assessed with a 24-h dietary recall and 3-d food record (food log), during each visit that were analyzed by Food Processor Nutrition Analysis Software. The compliance of the consumption of the DP or P was evaluated with the number of empty packages returned at the following visit. Physical activity was assessed using the International physical activity questionnaire (IPAQ).

Eligibility criteria: Inclusion Criteria:

* clinical diagnosis of type 2 diabetes
* Male or female.
* Adults between 30 and 60 years old.
* BMI of 25 to 39.9 kg / m².
* Pharmacological treatment with metformin, a combination of metformin and glibenclamide.
* Evolution of the type 2 diabetes of 4 ± 3 years.
* Patients who knew how to read and write.
* Signature of informed consent.

Exclusion Criteria:

* Diseases that produce secondary obesity.
* Cardiovascular event.
* Weight loss\> 3 kg in the last 3 months after the evaluation of the criteria.
* Catabolic diseases such as cancer and acquired immunodeficiency syndrome.
* Gravidity status.
* Positive smoking.
* Treatment with antihypertensive drugs
* Treatment with other hypoglycemic agents that were not metformin
* Treatment with statins, fibrates or other drugs to control dyslipidemia, 6 months before the start of the protocol.
* Any drug or medication that activates intestinal motility
* Use of laxatives or antispasmodics 4 weeks before the study
* Treatment with antibiotics 6 months before the study
* Use of steroids, chemotherapy, immunosuppressant or radiotherapy.
* Uncontrolled type 2 diabetes, ( HbA1c concentration ≥ 9.9%)
* Fasting glucose ≥ 220 mg / dL
* Fasting cholesterol ≥ 240 mg / dL
* Fasting triglycerides ≥ 350 mg / dL
* Serum creatinine in women\> 1.2 mg / dL in men\> 1.3 mg / d

Primary outcomes:
measure: intestinal microbiota
timeFrame: Change from baseline gut microbiota at three months after the dietary intervention
Secondary outcomes:
measure: Glucose metabolism profile
timeFrame: Change from baseline serum glucose at three months after dietary intervention
measure: Glucose metabolism profile
timeFrame: Change from baseline serum insulin at three months after dietary intervention
measure: Glucose metabolism profile
timeFrame: Change from baseline plasma HbA1c at three months after dietary intervention
measure: Lipid metabolism profile
timeFrame: Change from baseline serum triglycerides at three months after dietary intervention
measure: Lipid metabolism profile
timeFrame: Change from baseline serum total cholesterol at three months after dietary intervention
measure: Lipid metabolism profile
timeFrame: Change from baseline serum LDL cholesterol at three months after dietary intervention
measure: Lipid metabolism profile
timeFrame: Change from baseline serum HDL cholesterol at three months after dietary intervention
measure: Lipid metabolism profile
timeFrame: Change from baseline plasma free fatty acids at three months after dietary intervention
measure: metabolomic profile
timeFrame: Change from baseline plasma betaine at three months after dietary intervention
measure: metabolomic profile
timeFrame: Change from baseline plasma choline at three months after dietary intervention
measure: metabolomic profile
timeFrame: Change from baseline plasma TMAO at three months after dietary intervention
measure: metabolomic profile
timeFrame: Change from baseline plasma BCAA at three months after dietary intervention
measure: inflammatory profile
timeFrame: Change from baseline plasma LPS at three months after dietary intervention
measure: inflammatory profile
timeFrame: Change from baseline serum CRP at three months after dietary intervention
Other outcomes:
Locations:
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Nimbe Torres, PhD
role: PRINCIPAL_INVESTIGATOR
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