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

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

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.

Study Overview

• Status: Completed
• Conditions: Increased Insulin
• Intervention / Treatment: Other: Andrographis Paniculata Ext

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • Faculty of Medicine, Universitas Indonesia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 year old until 60 year old
2. Normal glucose tolerance subject or prediabetes
3. The kidney function (creatinine) and liver function (SGPT) in range normal
4. Subject has signed agreement (informed consent)

Exclusion Criteria:

1. Pregnant
2. Feeding baby
3. Subject has comorbide or chronic disease uncontrolled
4. Subject has cancer
5. Subject consume medication influenced blood glucose such as steroid an suplement
6. Insulin dependent diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Indonesia University
• Investigators: Principal Investigator: Tri Juli Edi Tarigan, MD, Fakultas Kedokteran Universitas Indonesia

Publications and helpful links

General Publications

• Wedick NM, Pan A, Cassidy A, Rimm EB, Sampson L, Rosner B, Willett W, Hu FB, Sun Q, van Dam RM. Dietary flavonoid intakes and risk of type 2 diabetes in US men and women. Am J Clin Nutr. 2012 Apr;95(4):925-33. doi: 10.3945/ajcn.111.028894. Epub 2012 Feb 22.
• Tarigan TJE, Purwaningsih EH, Yusra, Abdullah M, Nafrialdi, Prihartono J, Saraswati MR, Subekti I. Effects of Sambiloto (Andrographis paniculata) on GLP-1 and DPP-4 Concentrations between Normal and Prediabetic Subjects: A Crossover Study. Evid Based Complement Alternat Med. 2022 Jan 15;2022:1535703. doi: 10.1155/2022/1535703. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2017
• Primary Completion (Actual): May 2, 2018
• Study Completion (Actual): May 2, 2018

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: March 5, 2018
• First Posted (Actual): March 6, 2018

Study Record Updates

• Last Update Posted (Actual): September 14, 2020
• Last Update Submitted That Met QC Criteria: September 10, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Platelet Aggregation Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Andrographolide
• Other Study ID Numbers: IndonesiaU-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No