Investigate the Efficacy and Safety of Low-Glu in Patients Newly Diagnosed With Type II Diabetes Mellitus

Type2 Diabetes Mellitus Clinical Trial

Official title:

A Phase II, Randomized, Double Blind, Double Dummy, Active-Controlled Clinical Trial to Investigate the Efficacy and Safety of Low-Glu in Patients Newly Diagnosed With Type II Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05343767
• Other study ID #: NW_Low-Glu_14122016
• Status: Completed
• Phase: N/A
• Start date: September 12, 2018
• Est. completion date: May 30, 2021

Study information

• Verified date: April 2022
• Source: Natural Wellness Egypt
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ficus deltoidea leaves, Cinnamomum cassia and Black seed powdered extract have long been used for the treatment of type 2 diabetes mellitus.

Description:

Diabetes Mellitus (DM), commonly referred to as Diabetes is defined by World Health Organization (WHO) as a group of metabolic disorders characterized by chronic Hyperglycemia resulting from defects in insulin secretion, insulin action or both. Long-term organ damage, organ dysfunction and organ failure are associated with the chronic Hyperglycemia of Diabetes. Possible Diabetes complications can be classified into two major categories; macrovascular and microvascular including Ischemic Heart Disease (IHD), Peripheral Vascular Disease (PVD), and Cerebrovascular Disease (CVD) "macrovascular", and Nephropathy, Retinopathy, and Neuropathy "microvascular" resulting in organ and tissue damage in almost one third to one half of population with diabetes. According to the International Diabetes Federation (IDF), the three main types of Diabetes are Type 1 Diabetes, Type 2 Diabetes and Gestational Diabetes. Type 1 DM, formerly described as "Insulin Dependent Diabetes Mellitus" (IDDM) results from β-cells destruction, usually leading to absolute deficiency of insulin. Type 2 DM formerly described as "Non-Insulin-Dependent Diabetes Mellitus" (NIDDM) results from a progressive insulin secretory defect on the background of insulin resistance. Gestational Diabetes, which appears during pregnancy, is associated with increasing the risk of developing type 2 Diabetes in both mother and child later in life. Diabetes is a rapidly growing health concern in both developed and developing nations and its prevalence is continuously increasing worldwide. Globally, in 2014, approximately 422 million adults were having diabetes, with type 2 making up about 91%of the cases. In 2015, according to IDF, an estimated 415 million adults were having diabetes along with an estimated 318 million adults with impaired glucose tolerance. Both WHO and IDF predict that by 2030, this number will be doubled. In 2016 the WHO global report on Diabetes stated that the prevalence of Diabetes has increased faster in low- and middle-income countries than in high-income countries. Type 2 Diabetes is characterized by insulin resistance and/or abnormal insulin secretion, either of which may predominate. It is associated with several metabolic defects such as obesity, hypertension, and dyslipidemia, which contribute to the very high rate of cardiovascular morbidity and mortality. Medicinal herbs were used to treat a wide range of diseases long time before the birth of conventional medicine systems. The World Health Organization (WHO) has listed 21,000 plant names, which are used for medicinal purposes around the world, so despite the fact that medicinal herbs are at times misconceived as being unscientific, their continual existence proves they are able to be alternatives or complementary to conventional drugs at some point. Specifically, Ficus deltoidea leaves, Cinnamomum cassia L. powdered Extract and Black seed powdered extract have been used for the treatment of Diabetes Mellitus and other medical conditions for over 2000 years. Ficus deltoidea is an evergreen shrub reaching to 2 meters of height, with whitish grey bark, broadly spoon-shaped to obovate leaves and spherical or round figs. Over the years, it has been used to treat many diseases such as; Diabetes Mellitus, Hypertension, Hyperlipidemia and Gout. Numerous studies were conducted over the past years to assess the safety of Ficus deltoidea, Cinnamomum cassia L. powdered extract and Black seed powdered extract and their efficacy in treating type 2 Diabetes Mellitus. As the available data on NW Low-Glu efficacy, safety and dosing regimen is not enough, this study will be conducted to compare the hypoglycemic effect of two doses of a herbal medicinal product of ficus and Cinnamomum cassia L. powdered Extract + Black seed powdered extract (NW Low-Glu) to that of Metformin as measured by the mean change in HbA1c levels in patients newly diagnosed with type II diabetes mellitus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 198
• Est. completion date: May 30, 2021
• Est. primary completion date: May 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Able and willing to provide written informed consent.

2. Males and females aged between 18 and 65 years of age.

3. Newly diagnosed with type II diabetes mellitus patients as per the following criteria (FBG = 126 mg/dl) or, 2h- post prandial = 200 mg/dl during OGTT or, HbA1c = 6.5%

4. Anti-diabetic treatment naïve patients.

5. Able and willing to perform SMBG and to complete subject diaries.

Exclusion Criteria:

1. Pregnant or lactating women; women of childbearing potential must agree to use an accepted method of contraception during the course of the study and for 1 month after their last dose of study drug.

2. Patients with BMI > 40 Kg/m2 or BMI < 18.5 Kg/m2.

3. eGFR <60 mL/min/1.73 m2 (measured by the CKD-EPI equation) 3.

4. History of Positive human immunodeficiency virus, hepatitis B surface antigen (HBsAG), or hepatitis C antibody test.

5. History of type I diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes such as Cushing's syndrome or acromegaly.

6. History of diabetic complications such as diabetic ketoacidosis, lactic acidosis or state of hyperosmolar hyperglycemia, diabetic proliferative retinopathy, or severe diabetic neuropathy (requiring treatment with antidepressants or opioids) and history of decompensated diabetes (polyuria, polydipsia, nocturia, fatigue).

7. History of chronic gastrointestinal (GI) conditions that could impede gastric emptying or potentially affect the interpretation of the study data.

8. History of weight loss surgery or weight loss procedure involving the GI tract, such as gastric bypass, gastric stapling, or gastric banding.

9. History of an eating disorder (e.g., bulimia, anorexia).

10. History of malignancy (except treated basal or squamous cell skin cancer) within 5 years prior to screening.

11. History of significant cardiovascular disease (such as congestive heart failure, myocardial infarction, coronary disease) or uncontrolled hypertension.

12. History of clinically significant renal or liver disease.

13. Receipt of an investigational drug within 30 days prior to screening, or active enrollment in another investigational medication or device trial.

14. Known or suspected allergy to the trial products.

15. Any condition, in the judgment of the investigator, that would interfere with the patient's ability to comply with all study requirements or that would place the patient at unacceptable risk by his/her participation in the study.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type2 Diabetes Mellitus

Intervention

Dietary Supplement:
• Natural Wellness Low-Glu low dose
The contents of 4 capsules of NW Low-Glu were equally distributed and inserted into 6 capsules size 0, and administered in 3 daily doses
• Natural Wellness Low-Glu high dose
The contents of 5 capsules of NW Low-Glu were equally distributed and inserted into 6 capsules size 0, and administered in 3 daily doses

Other:
• Metformin
A total dose of 2000 mg was administered per day.

Locations

Country	Name	City	State
Egypt	Natural Welness Egypt	Cairo	Nasr City

Sponsors (1)

Lead Sponsor	Collaborator
Natural Wellness Egypt

Country where clinical trial is conducted

Egypt, 

References & Publications (27)

Adam Z, Khamis S, Ismail A, Hamid M. Ficus deltoidea: A Potential Alternative Medicine for Diabetes Mellitus. Evid Based Complement Alternat Med. 2012;2012:632763. doi: 10.1155/2012/632763. Epub 2012 Jun 3. — View Citation

Akilen R, Tsiami A, Devendra D, Robinson N. Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr. 2012 Oct;31(5):609-15. doi: 10.1016/j.clnu.2012.04.003. Epub 2012 May 12. Review. — View Citation

Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998 Jul;15(7):539-53. — View Citation

American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021 Jan;44(Suppl 1):S111-S124. doi: 10.2337/dc21-S009. Review. — View Citation

Askari G, Rouhani MH, Ghaedi E, Ghavami A, Nouri M, Mohammadi H. Effect of Nigella sativa (black seed) supplementation on glycemic control: A systematic review and meta-analysis of clinical trials. Phytother Res. 2019 May;33(5):1341-1352. doi: 10.1002/ptr.6337. Epub 2019 Mar 14. — View Citation

Bamosa A, Kaatabi H, Badar A, Al-Khadra A, Al Elq A, Abou-Hozaifa B, Lebda F, Al-Almaie S. Nigella sativa: A potential natural protective agent against cardiac dysfunction in patients with type 2 diabetes mellitus. J Family Community Med. 2015 May-Aug;22(2):88-95. doi: 10.4103/2230-8229.155380. — View Citation

Bunawan H, Amin NM, Bunawan SN, Baharum SN, Mohd Noor N. Ficus deltoidea Jack: A Review on Its Phytochemical and Pharmacological Importance. Evid Based Complement Alternat Med. 2014;2014:902734. doi: 10.1155/2014/902734. Epub 2014 Mar 18. Review. — View Citation

Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther. 2008 Nov;88(11):1322-35. doi: 10.2522/ptj.20080008. Epub 2008 Sep 18. — View Citation

Choo CY, Sulong NY, Man F, Wong TW. Vitexin and isovitexin from the Leaves of Ficus deltoidea with in-vivo a-glucosidase inhibition. J Ethnopharmacol. 2012 Aug 1;142(3):776-81. doi: 10.1016/j.jep.2012.05.062. Epub 2012 Jun 7. — View Citation

Corner E. The complex of Fixcus Deltoidea ; A recent invasion of the sunda shelf. Philos Trans R Soc London B, Biol Sci. 1969 Nov;256(808):281-317.

Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med. 2009 Sep-Oct;22(5):507-12. doi: 10.3122/jabfm.2009.05.080093. — View Citation

Daryabeygi-Khotbehsara R, Golzarand M, Ghaffari MP, Djafarian K. Nigella sativa improves glucose homeostasis and serum lipids in type 2 diabetes: A systematic review and meta-analysis. Complement Ther Med. 2017 Dec;35:6-13. doi: 10.1016/j.ctim.2017.08.016. Epub 2017 Aug 30. Review. — View Citation

Draman S, Aris M, Razman, SFU A, H A, AR NA, et al. Mas Cotek (Ficus deltoidea): A Possible Supplement for Type II Diabetes: (A Pilot Study). Pertanika J Trop Agric Sci. 2012;35(1):93-102.

Dugoua JJ, Seely D, Perri D, Cooley K, Forelli T, Mills E, Koren G. From type 2 diabetes to antioxidant activity: a systematic review of the safety and efficacy of common and cassia cinnamon bark. Can J Physiol Pharmacol. 2007 Sep;85(9):837-47. Review. — View Citation

Edelman SV. Type II diabetes mellitus. Adv Intern Med. 1998;43:449-500. Review. — View Citation

Hakiman M, Maziah M. Non enzymatic and enzymatic antioxidant activities in aqueous extract of different Ficus deltoidea accessions. J Med Plants Res. 2009;3(3):120-31.

Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, Blonde L, Bray GA, Cohen AJ, Dagogo-Jack S, Davidson JA, Einhorn D, Ganda OP, Garber AJ, Garvey WT, Henry RR, Hirsch IB, Horton ES, Hurley DL, Jellinger PS, Jovanovic L, Lebovitz HE, LeRoith D, Levy P, McGill JB, Mechanick JI, Mestman JH, Moghissi ES, Orzeck EA, Pessah-Pollack R, Rosenblit PD, Vinik AI, Wyne K, Zangeneh F. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY--CLINICAL PRACTICE GUIDELINES FOR DEVELOPING A DIABETES MELLITUS COMPREHENSIVE CARE PLAN--2015--EXECUTIVE SUMMARY. Endocr Pract. 2015 Apr;21(4):413-37. — View Citation

IDF. IDF Diabetes Atlas · Seventh Edition. 2015.

Jia Q, Liu X, Wu X, Wang R, Hu X, Li Y, Huang C. Hypoglycemic activity of a polyphenolic oligomer-rich extract of Cinnamomum parthenoxylon bark in normal and streptozotocin-induced diabetic rats. Phytomedicine. 2009 Aug;16(8):744-50. doi: 10.1016/j.phymed.2008.12.012. Epub 2009 May 22. — View Citation

Monnier L, Colette C. Target for glycemic control: concentrating on glucose. Diabetes Care. 2009 Nov;32 Suppl 2:S199-204. doi: 10.2337/dc09-S310. Review. — View Citation

Pan SY, Pan S, Yu ZL, Ma DL, Chen SB, Fong WF, Han YF, Ko KM. New perspectives on innovative drug discovery: an overview. J Pharm Pharm Sci. 2010;13(3):450-71. Review. — View Citation

Prakash B, Singh P, Yadav S, Singh SC, Dubey NK. Safety profile assessment and efficacy of chemically characterized Cinnamomum glaucescens essential oil against storage fungi, insect, aflatoxin secretion and as antioxidant. Food Chem Toxicol. 2013 Mar;53:160-7. doi: 10.1016/j.fct.2012.11.044. Epub 2012 Dec 5. — View Citation

Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6. — View Citation

Sulaiman MR, Hussain MK, Zakaria ZA, Somchit MN, Moin S, Mohamad AS, Israf DA. Evaluation of the antinociceptive activity of Ficus deltoidea aqueous extract. Fitoterapia. 2008 Dec;79(7-8):557-61. doi: 10.1016/j.fitote.2008.06.005. Epub 2008 Jul 10. — View Citation

Tauseef Sultan M, Butt MS, Anjum FM. Safety assessment of black cumin fixed and essential oil in normal Sprague Dawley rats: Serological and hematological indices. Food Chem Toxicol. 2009 Nov;47(11):2768-75. doi: 10.1016/j.fct.2009.08.011. Epub 2009 Aug 21. — View Citation

WHO. Global report on diabetes. 2016.

Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001 Dec 13;414(6865):782-7. Review. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory outcome	To explore the effect of NW Low-Glu on Beta cell function in patients newly diagnosed with type II diabetes mellitus by assessing through HOMA-ß modeling.	12 weeks
Other	Measuring the activity of alpha-glucosidase enzyme to investigate the effect of NW Low-Glu on intestinal glucose absorption	To investigate the effect of NW Low-Glu on intestinal glucose absorption by measuring the activity of alpha-glucosidase enzyme.	12 weeks
Other	To investigate the effect of NW Low-Glu on weight.	To investigate the effect of NW Low-Glu on weight by comparing patients' weight before and after the intervention	12 weeks
Primary	To compare the hypoglycemic effect of two doses of a herbal medicinal product (NW Low-Glu) to that of Metformin as measured by the mean change in HbA1c levels in patients newly diagnosed with type II diabetes mellitus.	Comparing the mean change in HbA1c levels between each experimental arm and active-control arm	12 weeks
Secondary	To measure the incidence of hypoglycemia events and other adverse events in patients newly diagnosed with type II diabetes mellitus (Safety)	Comparing the mean change in fasting plasma glucose levels between each experimental arm and active-control arm	12 weeks
Secondary	To compare the mean change in the 2h-post prandial glucose levels between each experimental arm and active-control arm (efficacy)	To compare the mean change in the 2h-post prandial glucose levels between each experimental arm and active-control arm.	12 weeks