Efficacy and safety of two Ayurvedic dosage forms for allergic rhinitis: Study protocol for an open-label randomized controlled trial.

BACKGROUND: Allergic rhinitis (AR) is an immune response of the nasal mucosa to airborne allergens and involves nasal congestion, watery nasal discharge, itching of the nose, and sneezing. The symptoms of allergic rhinitis may significantly affect a patient's quality of life and can be associated with conditions such as fatigue, headache, cognitive impairment, and sleep disturbances. Various complementary and alternative medicine treatments have been used for this condition in clinical practice. The Ayurveda system of medicine is the most common complementary medicine system practiced in Sri Lanka. The aim of this study is to examine the efficacy and safety of a decoction used in traditional Ayurveda for allergic rhinitis and its ready- to-use freeze dried formulation in comparison to an antihistamine over a period of 4 weeks on relief of symptoms in allergic rhinitis. STUDY DESIGN: This is a three-arm, open-label, non-inferiority, randomized controlled clinical trial enrolling patients with AR. Tamalakyadi decoction containing 12 ingredients (TMD12), used in traditional Ayurveda and its freeze-dried formulation are the test products. The efficacy and safety of the two Ayurvedic dosage forms will be tested against the antihistamine loratadine. Patients with symptoms of AR will be allocated randomly into the three arms after a 1-week run-in period and the medications will be given orally for 28 days. Total Nasal symptom Score (TNSS) of the patients will be used as the primary efficacy endpoint. TNSS will be recorded and compared between the three arms prior to visit 1, at the end of 28 days, and end of the first and second months of follow-up. Symptom scores of daytime nasal symptoms, night time nasal symptoms, non-nasal symptoms and health-related quality of life questionnaire are used as secondary end points. DISCUSSION: This clinical trial will be able to provide evidence-based scientific data on Ayurvedic dosage form, TMD12, and the freeze-dried formulation in the treatment of allergic rhinitis. This trial is expected to develop capacity to scientifically evaluate various Ayurvedic treatments that are claimed to have efficacy in treatment of various disease conditions. TRIAL REGISTRATION: ISRCTN18149439 (6 May 2019).

Evaluation of pharmacodynamic properties and safety of Cinnamomum zeylanicum (Ceylon cinnamon) in healthy adults: a phase I clinical trial.

BACKGROUND: Cinnamon is considered as a treatment for many ailments in native medicine. Evidence suggests that Cinnamomum zeylanicum (CZ) has anti-microbial, anti-parasitic, anti-oxidant, blood glucose lowering properties and beneficial cardiovascular effects. The present study aims to evaluate Pharmacodynamic properties and safety of CZ in healthy adults using a Phase I Clinical Trial. METHODS: This phase I clinical trial was conducted at the Department of Pharmacology, Faculty of Medicine, University of Colombo, Sri Lanka. Thirty healthy adults were recruited for the study, conducted for a period of 3 months, with the dose of CZ (water extract) increased at monthly intervals (85 mg, 250 mg and 500 mg). Data collection was carried out at baseline and during each monthly follow up visit. Anthropometric, clinical and biochemical assessments were done at baseline and during follow up. Adverse effects and drug compliance was also evaluated. RESULTS: Twenty eight subjects completed the three months follow up. Mean age was 38.8 ± 10.4 years and 50% were males. There were no significant changes in the anthropometric parameters during the three months follow up. Both systolic and diastolic blood pressure reduced significant during the 1st month and this reduction was sustained throughout follow up. Full blood count, renal function tests, liver function tests, fasting blood glucose, HDL-c, VLDL-d and triglycerides remained within the normal range without any significant alteration during the 3 months. A significant reduction in the TC (p < 0.05) and LDL-c (p < 0.001) was noted at the end of the 3 months follow up period. There were no serious adverse effects (including hypersensitivity) noted. In two participants dyspepsia necessitated the discontinuation of study participation. Drug compliance was between 85 and 95% during the study period. CONCLUSIONS: This is the first phase I clinical trial in health adults evaluating efficacy and safety of CZ. Our results demonstrate no significant side effects and toxicity of CZ, including hepatotoxicity and anti-coagulation properties. CZ demonstrated beneficial anti-hyperlipidaemic and blood pressure lowering effects among healthy adults. Further studies with larger samples and longer durations may be able to elucidate other side effects and better describe the pharmacodynamic properties. TRIAL REGISTRATION: SLCTR/2013/001 (Sri Lanka Clinical Trials Registry: http://www.slctr.lk/trials/106 ) (Date of Registration: 01/01/2013).

Cinnamomum zeylanicum (Ceylon cinnamon) as a potential pharmaceutical agent for type-2 diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Previous studies have explored the anti-diabetic effects of Cinnamomum cassia extract in vivo and in vitro. However, there are no studies at present exploring the effects of the indigenous species of Sri Lankan cinnamon (Cinnamomum zeylanicum) in patients with diabetes mellitus. The present study aims to evaluate the potential effects of Cinnamomum zeylanicum extract as a pharmaceutical agent in patients with type-2 diabetes mellitus. METHODS/DESIGN: The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 4 months at the Medical Clinic, University Medical Unit, National Hospital of Sri Lanka. A total of 210 subjects with diabetes, in three equal groups, will be recruited for the study. The patients will be randomized in a 1:1:1 ratio according to the method of block randomization and the subjects will be randomly and equally assigned into two test groups (n = 70 each) and one placebo group (n = 70). The population will be stratified at randomization based on age, gender and disease severity. The treatment drug is a capsule containing Cinnamomum zeylanicum extract as the active ingredient and the placebo capsule will contain lactose monohydrate. Two doses of Cinnamomum zeylanicum extracts (250 mg and 500 mg of the cinnamon extract) will be used. The study drugs will be double blinded to both investigators and participants. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 2 months (visit 2), 3 months (visit 3) and 4 months (visit 4). The following primary outcome measures will be evaluated: glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG) and serum insulin. Secondary outcome measures include: Body Mass Index (BMI) and other anthropometric parameters, blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TAG). Data will be analyzed using SPSS version 14. DISCUSSION: We describe the protocol for a clinical trial design evaluating the effects of Cinnamomum zeylanicum (Ceylon cinnamon) in patients with type-2 diabetes mellitus. The result of the present study, positive or negative, should provide a step change in the evidence guiding current and future policies regarding the use of cinnamon dietary supplementation in patients with diabetes. TRIAL REGISTRATION: Sri Lanka Clinical Trials Registry (SLCTR), identifier: SLCTR/2017/010 ( http://slctr.lk/trials/714 ). Registered on 5 April 2017; study protocol version 3.1 21 March 2017.

Medicinal properties of 'true' cinnamon (Cinnamomum zeylanicum): a systematic review.

BACKGROUND: In traditional medicine Cinnamon is considered a remedy for respiratory, digestive and gynaecological ailments. In-vitro and in-vivo studies from different parts of the world have demonstrated numerous beneficial medicinal effects of Cinnamomum zeylanicum (CZ). This paper aims to systematically review the scientific literature and provide a comprehensive summary on the potential medicinal benefits of CZ. METHODS: A comprehensive systematic review was conducted in the following databases; PubMed, Web of Science, SciVerse Scopus for studies published before 31st December 2012. The following keywords were used: "Cinnamomum zeylanicum", "Ceylon cinnamon", "True cinnamon" and "Sri Lankan cinnamon". To obtain additional data a manual search was performed using the reference lists of included articles. RESULTS: The literature search identified the following number of articles in the respective databases; PubMed=54, Web of Science=76 and SciVerse Scopus=591. Thirteen additional articles were identified by searching reference lists. After removing duplicates the total number of articles included in the present review is 70. The beneficial health effects of CZ identified were; a) anti-microbial and anti-parasitic activity, b) lowering of blood glucose, blood pressure and serum cholesterol, c) anti-oxidant and free-radical scavenging properties, d) inhibition of tau aggregation and filament formation (hallmarks of Alzheimer's disease), e) inhibitory effects on osteoclastogenesis, f) anti-secretagogue and anti-gastric ulcer effects, g) anti-nociceptive and anti-inflammatory activity, h) wound healing properties and i) hepato-protective effects. The studies reported minimal toxic and adverse effects. CONCLUSIONS: The available in-vitro and in-vivo evidence suggests that CZ has many beneficial health effects. However, since data on humans are sparse, randomized controlled trials in humans will be necessary to determine whether these effects have public health implications.

Zinc supplementation in pre-diabetes: study protocol for a randomized controlled trial.

BACKGROUND: The number of people with diabetes is increasing worldwide, especially in developing South Asian countries. Therefore, preventing diabetes at the early stages has become an important issue. Recent clinical trials, systematic reviews, and meta-analysis have shown that zinc has beneficial effects on glycemic and metabolic control in those with diabetes. The present study is designed to evaluate the effects of zinc supplementation on glycemic control and other metabolic parameters in those with pre-diabetes. METHODS/DESIGN: The study will be conducted as a randomized, double-blind, placebo-controlled clinical trial for a period of 12 months at the Faculty of Medicine, University of Colombo, Sri Lanka. The study has been approved by the Ethics Review Committee of Faculty of Medicine, University of Colombo (EC/11/189). A total of 200 adults (age 18-60 years) with pre-diabetes will be recruited for the study. They will be stratified according to age, gender, and body mass index and randomly assigned into the test and placebo groups on a 1:1 ratio. The zinc capsules, each weighing 456 mg, will contain the following ingredients:zinc sulfate monohydrate 55.096 mg (elemental zinc 20 mg), lactose monohydrate 399.504 mg, and stearic acid 1.400 mg. The placebo capsule with the same weight will be comprised of lactose monohydrate 454.600 mg and stearic acid 1.400 mg. The subjects will receive either zinc 20 mg capsules or placebo daily for a period of 12 months. The study drugs will be double blinded to both investigators and subjects. The visits and the evaluations will be done as follows: screening (visit 0), 1 month (visit 1), 3 month (visit 2), 6 month (visit 3), and 12 month (visit 4). The following primary outcome measures will be evaluated:fasting plasma glucose (FPG), post oral glucose tolerance test (OGTT), serum insulin, HbA1c, total/low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol, triglycerides, serum zinc, and appetite using a visual analog scale. Secondary outcome measures include: blood pressure, anthropometry, and dietary assessment using a validated food frequency questionnaire. Data will be analyzed using SPSS v16. DISCUSSION: The present protocol will aim to establish the beneficial effects of zinc supplementation on disease progression in those with pre-diabetes and also establish its effectiveness in the prevention of diabetes mellitus. TRIAL REGISTRATION: Sri Lanka Clinical Trial Registry: SLCTR/2012/010.