Synbiotic Therapy on Intestinal Microbiota and Insulin Resistance in Obesity

Phase 4

Completed

• Conditions: Insulin Resistance; Obesity
• Interventions: Drug: Placebo; Dietary Supplement: Synbiotic (Rillus)

• Registration Number: NCT04642482
• Lead Sponsor: Hasanuddin University

Brief Summary

Background :

There is a plausible relationship between microbial gut and insulin resistance. Intervention to prevent insulin resistance by modifying the microbial gut has been proposed but limited studies demonstrates the expected impact. One of the possible way to manipulate the microbial gut is the administration of synbiotic (prebiotic and probiotic).

Objective :

This study aim to address the impact of synbiotic administration to the microbial gut and insulin resistance.

Brief Methodology :

A Quasi Experimental study with multiple arms is conducted to healthy participants. All subjects will undergo a microbial gut taxonomic analysis using faecal sample and blood examination to determine the insulin resistance status (using Homeostatic Model Assessment for Insulin Resistance/HOMA-IR approach). Synbiotic will be given to intervention arm and active comparator will use maltodextrin. Repeated measurement will be conducted after 8 weeks and 12 weeks from the day of administration.

Hypothesis : A superiority trial hypothesis is applied, assuming that the synbiotic group will demonstrates higher variety of microbial gut and lower HOMA-IR level

Detailed Description

Study Location :

This study will recruit the healthy participants from the university

Target Population:

Healthy Participants

General Study Design :

Quasi Experimental study with a comparator

Sample Size calculation :

Difference between two means of HOMA IR from pilot data (7) and standard deviation 2.9, with 5% Type I error, and 80% Power yielded a total of 16 participants for two arms

Management of Sample:

1. Faecal Sample handling

1. Patient should undergo 8 hours of fasting prior to faecal examination

2. DNA Extraction

3. Lysate preparation and centrifuge faecal sample

4. Mixing lysate with sample

5. Column wash

6. DNA elution

7. DNA storing

8. DNA sequencing and analysis

9. taxonomical analysis

2. Fasting blood glucose

1. Patient should undergo 8 hours of fasting prior to Fasting blood glucose

2. Blood is taken from cubital vein

3. Spectrometry is conducted based on the NADPH formation from the equation below

D-glucose+ATP -----\> Glucose-6-phospate+ADP Glucose-6-phospate+NAD ---- G-6-PDH ---\> D-Gluconate-6 phospate+NADH+H

3. Insulin level

1. Centrifuge blood to obtain the serum

2. The monoclonal anti-insulin antibody is given to the serum

3. detection is based on the anti-insulin antibody and insulin complex formation

4. Homeostatic Model Assessment for Insulin Resistance/ HOMA-IR value is calculated from glucose level multiply by insulin level and divided by 405.

Protection for adverse event

1. All subjects are given the consent regarding the potential harm of synbiotic administration

2. All subjects will follow the protocol of reporting the any adverse event (most likely, severe constipation)

3. All subjects will be treated accordingly and hospitalisation if needed.

Statistical Analysis

1. General Analysis : Intention To Treat (ITT)

2. Propensity Score Matching will be conducted prior to intervention

3. A repeated measure ANOVA will be performed, whereas Generalized Linear Mixed Model treating the intervention as dummy variable will be performed if ANOVA assumptions can not be fulfilled.

Study Timeline

• Study Start: 2019-09-24
• Primary Completion: 2019-12-26
• Study Completion: 2020-09-01
• Status Verified: 2020-11
• Study First Submitted: 2020-11-17
• Study First Submitted QC: 2020-11-23
• Last Update Submitted: 2020-11-23
• Study First Posted: 2020-11-24
• Last Update Posted: 2020-11-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Age above 18 years old
2. Not receive antibiotic prescription within the last 6 months

Exclusion Criteria

1. Taking medication that alters the blood sugar
2. Taking probiotic or synbiotic product (such as yogurt)
3. Participant who do not take the synbiotic intervention for more than 3 days consecutively
4. incomplete follow up examination results
5. Develop adverse effect

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	A powder of 5 gram maltodextrin is given as active comparator, taken orally.
Synbiotic	Synbiotic (Rillus)	A fine powder to be taken orally consists of Viable cell 1,0 x 10\^9 Colony Forming Unit of : * Lactobacillus plantarum 8,55 mg * Streptococcus thermophilus 8,55 mg * Bifidobacterium bifidum 2,55 mg * Fructooligosaccharide 480 mg * Additional components : isomalt, xylitol

Primary Outcome Measures

Name	Time	Method
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	Changes of HOMA IR value from baseline to 8 weeks	a value representing the insulin resistance yielded by multiplying the blood glucose value and insulin value, then divided by 405 (considering the unit of values are in mg/dL not mmol)

Trial Locations

Locations (1)

Faculty of Medicine, Muhammadiyah University; 🇮🇩 Makassar, South Sulawesi, Indonesia