The Effect of Andrographis Paniculata to GLP-1, Fasting Insulin, Insulin 2-h Post OGTT, and HOMA-IR

Study Overview
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Brief Summary
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Prevalence of type 2 diabetes have been increased, but medications had not been well, so that needed new alternatives. A new approach used in management of type 2 diabetes is incretin based therapy. Incretin hormone, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP), had producted in intestine due to carbohydrate intralumen. After had secreted, GLP-1 had degradated by DPP-4 enzyme till number and effect had been decreased. Decreasing of GLP-1 effect as main defect in type 2 diabetes. Andrographis paniculata (A. paniculata) as traditional treatment had known since years ago to have hypoglycemia effect. Extract of A. paniculata consists of andrographolid and flavonoid. Based on study of Wooten et al that flavonoid has hydroxyl to stimulate insulin's production through modulated GLP-1 receptor (GLP-1 receptor ligand). So the investigators need to study about The Effect of A. paniculata Extract to GLP-1, Fasting Plasma Insulin, Insulin concentrations measured during a standardized 2-h OGTT, and HOMA-IR.

Detailed Description
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Blood's participants will be examined fasting plasma insulin and glycated albumin (from fasting blood) and insulin measured during a standardized 2-h OGTT, DPP-4 enzyme, and GLP-1 (from standardized 2-h OGTT blood). Then, complete urinalysis test. Participants will be randomized to be two groups are group have been intervenced by capsules of A. paniculata or group placebo. Each group will be explained about procedure to consume capsules A. paniculata or placebo for 14 days, storage procedures, and the way to contact the investigators if adverse event happened. The investigators will contact participants to remember the schedule to consume capsules A. paniculata, ask whether the side effects or not, and ask the result of self monitoring blood glucose every three days by glucose meter have been given. Before day 12th, participants will be contacted to come in visit 2nd. In visit 2nd (day 15th) will be done anamneses, assessment of compliance, reporting adverse event and side effect, physical examination, fasting plasma glucose test, fasting insulin, HOMA-IR, GA and complete urinalysis. Then, will be done standardized 2-h OGTT. Two hours later, it will be done plasma glucose level, insulin, DPP-4 enzyme, and GLP-1. Participants will be explained that they will not receive capsules of A. paniculata for 7 days (day 15th till 21th). This is called wash out. Participants will be explained about procedures to consume capsule of A. paniculata or placebo in day 22th till 35th. Before day 32th, participants will be contacted to come in visit 3rd (day 36th). In visit 3rd, will be done anamneses, assessment of compliance, reporting adverse event and side effect, physical examination, fasting plasma glucose test, fasting insulin, HOMA-IR, GA and complete urinalysis. Then, will be done standardized 2-h OGTT. Two hours later, it will be done plasma glucose level, insulin, DPP-4 enzyme, and GLP-1.

Official Title
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The Effect of Andrographis Paniculata to GLP-1, Fasting Insulin, Insulin 2-h Post OGTT, and HOMA-IR in Normal and Prediabetes Subject

Conditions
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Increased Insulin

Intervention / Treatment
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* Other: Andrographis Paniculata Ext


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 year old until 60 year old Normal glucose tolerance subject or prediabetes The kidney function (creatinine) and liver function (SGPT) in range normal Subject has signed agreement (informed consent) Exclusion Criteria: Pregnant Feeding baby Subject has comorbide or chronic disease uncontrolled Subject has cancer Subject consume medication influenced blood glucose such as steroid an suplement Insulin dependent diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Clinical Trials with Randomization, Double Blind, Crossover
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal subject experimental<br>Participants get Andrographis Paniculata Extract 550 mg, two capsules, twice a day, for 14 days. | Other: Andrographis Paniculata Ext<br>* Give the Androgaphis paniculata in prediabetes and normal subject for 14 days.<br>|
| Placebo Comparator: Normal subject placebo<br>Participants get placebo consist of Lactose 98%, Mg 2%, two capsules, twice a day, for 14 days. | Other: Andrographis Paniculata Ext<br>* Give the Androgaphis paniculata in prediabetes and normal subject for 14 days.<br>|
| Experimental: Prediabetes subject experimental<br>Participants get Andrographis Paniculata Extract 550 mg, two capsules, twice a day, for 14 days. | Other: Andrographis Paniculata Ext<br>* Give the Androgaphis paniculata in prediabetes and normal subject for 14 days.<br>|
| Placebo Comparator: Prediabetes subject placebo<br>Participants get placebo consist of Lactose 98%, Mg 2%, two capsules, twice a day, for 14 days. | Other: Andrographis Paniculata Ext<br>* Give the Androgaphis paniculata in prediabetes and normal subject for 14 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GLP-1 | Index analyzes incretin effect | A measure assesing change from baseline GLP-1 at 14 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Insulin | Index analyzes beta-cell secretion | A measure assesing change from baseline GLP-1 at 14 days. | 
| 2h-OGTT Insulin | Index analyzes beta-cell secretion after 2h-OGTT | A measure assesing change from baseline GLP-1 at 14 days. | 
| HOMA-IR | Index of insulin resistance | A measure assesing change from baseline GLP-1 at 14 days. | 
| Fasting plasma glucose level | Index analyzes beta-cell function | A measure assesing change from baseline GLP-1 at 14 days. | 
| 2h-OGTT plasma glucose level | Index analyzes beta-cell function after 2h-OGTT | A measure assesing change from baseline GLP-1 at 14 days. | 
| Dypeptidil Peptidase 4 (DPP-4) Enzyme | Index analyzes degradation of GLP-1 in Ileum | A measure assesing change from baseline GLP-1 at 14 days. | 
| Glycated Albumin | Index analyzes plasma glucose during 2 weeks | A measure assesing change from baseline GLP-1 at 14 days. |