Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202206531545729 Date of Registration: 15/06/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Clinical trial of various fractions from popular antidiabetic Nigerian herbs for the management of type 2 diabetes: a double-blind, randomized, placebo-controlled trial
Official scientific title Integrating phytochemical fractions of Nigerian herbs in orthodox diabetes care
Brief summary describing the background and objectives of the trial As of 2020, 6 million Nigerians are living with diabetes mellitus. In 2015 alone, 40,000 Nigerians died as a result of diabetes and its complications, a figure likened to a tip of an iceberg given that that two-thirds of diabetes cases in Nigeria are yet undiagnosed. As a result, the use of herbal medicine alone or alongside prescription drugs for its management is quite common in Nigeria and most African countries. Anisopus mannii is a native Nigerian herb called the "diabetes killer" as it is popularly used for the management of Type 2 diabetes. Using various cell lines, our group discovered that the phenolic acid fractions of this herb (PhAM) serves as an agonist for the glycolysis enzyme called phosphofructokinase 1. In mice, the PhAM protected beta cells from streptozotocin induced destruction, justifying the current aim of this trial to investigate the PhAM and other fractions of the herb, like the carotenoids and hydroxycinnamic acid fractions in patients with Type 2 diabetes. Another herb, the Dacryodes edulis seeds, a routinely used antidiabetic therapy in Nigeria have shown preliminary evidence as a candidate incretin-mimetic. We found that D. edulis seed methanolic extract (DME) contained therapeutic doses of chlorogenic acid, epicatechins, ferulic acid and caffeic acid that are well documented to elicit incretin effect. The D. edulis seeds stimulated GLP-1 and GIP secretions in alloxan models of type 2 diabetes. The seed extract was well tolerated in STC-1 cells and liver cells applied for the preclinical testing of the safety of this potential therapy. Hence, in this trial, an additional arm of participants with type 2 diabetes, will be administered with the D. edulis seed extract, and/or extracts from this herb.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Nutritional, Metabolic, Endocrine
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Other
Anticipated trial start date 01/12/2022
Actual trial start date
Anticipated date of last follow up 01/01/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 108
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using by using procedures such as coin-tossing or dice-rolling Sealed opaque envelopes Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Placebo 1 standard placebo capsule containing 300 mg starch per day. Placebo capsules are to be purchased from Novo Nordisk. 4 months Administration of placebo capsules to participants. Placebo group are participants randomized into the group and must be diagnosed with T2DM with fasting blood glucose between 150 – 200 mg/dl, Hb1Ac between 7-9%, and must be between 40 to 64 years old. T2DM must have persisted >1 year and not diet-controlled, must be taking standard diabetes treatment, prior to the beginning of the intervention, 54 Placebo
Experimental Group Intervention Group 40 mg of D. edulis seed aqueous extract encapsulated in gastric acid resistant enteric coat will be administered daily. The 40mg was determined as non-toxic dose during our preclinical trial. Four months We will administer the intervention to 30 participants randomized into the intervention group. The participants must be diagnosed with T2DM with fasting blood glucose between 150 – 200 mg/dl, Hb1Ac between 7-9%, and must be between 40 to 64 years old. T2DM must have persisted >1 year and not diet-controlled, must be taking standard diabetes treatment, prior to the beginning of the intervention, and must express consent to include this herbal treatment in their routine diabetes care. 54
Experimental Group Low dose PhAM 12 mg PhAM every 48h 6 months Patients with type 2 diabetes administered 12 mg PhAM every 48 h for 6 months 30
Experimental Group High dose PhAM 20 mg PhAM every 48h 6 months Patients with type 2 diabetes administered 20 mg PhAM, orally, every 48h for 6 months 30
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
The main inclusion criteria were: - Age between ≥ 40 years ≤ 75 years - Clinical diagnosis of T2D - On the spot HbA1c >6.5% - History of good compliance to first-line diabetes medications - History of diabetes >2 years. Smoking, pregnancy, breastfeeding, use of steroids or any immunosuppressive or immunomodulatory therapies, use of any herbal drugs within 2 months before trial commences, history of any other metabolic disease that complicates the pathological features of type 2 diabetes, active hepatitis b or c, HIV, tuberculosis, and systemic infections. - Subjects on selected oral medication with a narrow therapeutic window, such as warfarin, digoxin, tricyclic antidepressants, lithium, aminophylline, theophylline and anticonvulsants - History of chronic pancreatitis or idiopathic acute pancreatitis - Chronic malabsorption, regardless of etiology - History of Crohn’s disease, ulcerative colitis, or other inflammatory bowel disease - Treatment with glucose lowering agent(s) other than metformin as stated in the inclusion criteria in a period of 90 days before the screening visit. Middle Aged: 45 Year(s)-64 Year(s) 40 Year(s) 75 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/12/2022 Institutional Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
FOBS, Imo State University, Owerri Owerri 234 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome We are adopting two primary endpoints. The change from baseline to end of treatment (i.e., after 6 months of treatment) in both fasting blood glucose and glycated hemoglobin levels, HbA1C. Subjects who, after 16 weeks of treatment, achieve (yes/no) HbA1c <7% (53 mmol/mol) and less than 120 mg/dl fasting blood glucose levels. This will be measured weekly at the start of the intervention until after the four weeks measurement. If no adverse effect after the first month, the primary outcomes will be measured monthly
Secondary Outcome - Changes in incretin levels; glucagon-like peptide (GLP-1), and glucose insulinotropic polypeptide (GIP) levels from baseline compared to levels at the end of the intervention. - Changes in glucagon, C-peptide, and fasting insulin levels from baseline compared to levels at the end of the intervention. - Changes in beta-cell function (homeostatic model assessment index of beta-cell function (HOMA-B) from baseline compared to levels at the end of the intervention. - Changes in body mass index (BMI), blood pressure, mid-arm circumference, and polyuria. After every 4 weeks.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
College of Medicine Outpatient Center Imo State University Teaching Hospital Owerri Orlu Express Way Orlu Nigeria
Federal Medical Center Owerri Amakohia Owerri Imo State Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Tetfund National Research Funding N0 6 Zambezi Crescent, Off Aguiyi Ironsi Street Maitama Abuja Nigeria
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Imo State University Owerri Okigwe Road, Off Works Layout, Owerri Imo State Nigeria University
COLLABORATORS
Name Street address City Postal code Country
Professor Gabriel Oze Deanery, Faculty of Basic Medical Sciences, Imo State University Owerri Nigeria
Dr. Chidi Nosiri Department of Pharmacology, Abia State University, Uturu Abia Nigeria
Dr. Celestine Ekweogu Faculty of Basic Medical Sciences, Imo State University Owerri Nigeria
Dr. Justice Osuoha Monash University, Australia Melbourne Australia
Mrs. Chiamaka Adumekwe Department of Biochemistry, Imo State University, Owerri Owerri Nigeria
Professor Sylvia Santosa Department of Exercise Science, Kinetics, and Physiology, Concordia University Montreal Canada
Mr Uche Njoku Department of Biochemistry, University of Port Harcourt, Choba, Rivers State. Owerri Nigeria
Professor Fiona Gribble Institute of Metabolic Science, University of Cambridge, UK Cambridgeshire United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Peter Uchenna Amadi Peter_amadi@uniport.edu.ng +2348061159916 Department of Biochemistry, Imo State University, Owerri, Imo State
City Postal code Country Position/Affiliation
Owerri Imo State Nigeria Lecturer Imo State University Owerri
Role Name Email Phone Street address
Public Enquiries Peter Uchenna Amadi Peter_amadi@uniport.edu.ng +2348061159916 Department of Biochemistry, Imo State University, Owerri, Imo State
City Postal code Country Position/Affiliation
Owerri Nigeria Lecturer Imo State University Owerri
Role Name Email Phone Street address
Scientific Enquiries Peter Uchenna Amadi Peter_amadi@uniport.edu.ng +2348061159916 Department of Biochemistry, Imo State University, Owerri, Imo State
City Postal code Country Position/Affiliation
Owerri Nigeria Lecturer Imo State University Owerri
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data obtained through this study may be provided to qualified researchers with academic or research interest in diabetes. Data or samples shared will be coded, with no patient health information included. Approval of the request and execution of all applicable agreements like material transfer agreement are prerequisites to the sharing of data with the researchers making the request. Informed Consent Form 1 year after completion of the project Suitability for sharing Yes Discovery by potential users of the research data Data management team ensures designated staff work with PI’s to develop easily discoverable metadata with reasonable data-sharing agreements notice to potential users in administered, and to be deposited at widely accessible open access data repositories like Figshare and Mendeley depending on the funder’s data management policies. Governance of access Less sensitive information are made freely available at depositories, whereas decisions regarding access to data with considerable access restriction are subject to consideration by the data access committee (must include the PI except for when dead or clearly inaccessible) on receipt of an official request from a requester. Nonetheless, requests are denied without review if it compromises the confidentiality of study participants. The university research office management team exercises the right of oversight of data access and sharing. Open access journals with authors securing full copyright access are relied upon to disseminate and provide access to peer reviewed research data and supplementary files. The study team’s exclusive use of the data It is the policy of IMSU that the consideration of request for data access to public is made timely, as soon as data has been deposited in the database. However, a clause to grant the principal investigator exclusive access for up to 12 months is upheld within which the decision on access depending on the data value and needs relies on the discretion of the PI. Nevertheless, the university senate retains an overriding authority to the clause. Restrictions or delays to sharing, with planned actions to limit such restrictions Before study commencement, it is required to receive participants consent agreements with clear and detailed descriptions of plans to widely but procedurally circulate non sensitive details and outcomes. With these agreements in place, the delays to data sharing is mitigat
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
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Result URL Hyperlinks Link To Protocol
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