Evaluation of the analgesic activity of single and multiple oral doses of teneligliptin (20 mg/day), using hot air analgesiometer in healthy human volunteers: a randomized, double blind, placebo controlled, cross over study

Background DPP-4 inhibitors showed analgesic and anti-inflammatory activity in human and animal-studies. DPP-4 inhibitors improved nerve function and thermal nociception in animal models. Aim of the study was to explore analgesic activity of single and multiple doses of teneligliptin 20 mg/day using hot air analgesiometer in healthy human volunteers.Methods: After IEC approval and informed consent, subjects were randomized to receive either teneligliptin 20 mg or placebo in double-blinded manner with standard breakfast. Mean pain threshold and tolerance(sec) using hot air analgesiometer were recorded at baseline and 1 hr, 2 hrs post drug on day 1, for single dose study. Subsequently drugs were administered under supervision daily for 6 days and same procedure repeated on day8 for multiple-dose study. After 2 weeks washout, subjects crossed over in period 2 to receive other formulation and same procedure repeated to determine study parameters. Fasting blood-sugar (FBS) was monitored, ADRs recorded in CRF. Statistical analysis done with SPSS20.0.Results: Twelve-healthy subjects (8 males, 4 females) with mean age 33.08±4.69 years, mean BMI 22.6±1.37kg/m2 participated. Single dose teneligliptin produced significant increase in pain threshold (35.9%) and pain tolerance (25.1%) (p<0.001) at 1hour compared to baseline. With multiple doses, pain threshold increased by 37.1% and pain tolerance by 25.4% (p<0.001) at 1hour compared to baseline. The increase in pain threshold and tolerance values at 1 and 2 hours were similar. There was no significant change in pain threshold(p=0.4135) and tolerance (p=0.4476) at baseline on day1 and day 8. Placebo showed non-significant change in study parameters. Both treatments well tolerated. FBS of volunteers within normal limits during treatment period and no hypoglycemia reported.Conclusions: Results of our study suggest that teneligliptin20mg in healthy subjects demonstrated modest analgesic activity compared to baseline and placebo. Its role in painful diabetic conditions may be further explored

Evaluation of effect of highly standardized aqueous extract of roots and leaves of Withania somnifera on cold pressor test induced cardiovascular changes in healthy human subjects

Background: Stress is an important cardiovascular risk factor. Cold pressor test (CPT) is a simple, validated, non-invasive test used to measure stress induced changes in cardiovascular parameters. The objective of this study was to evaluate effect of Withania somnifera extract on cold pressor stress test induced changes on cardiovascular parameters and aortic wave reflections in healthy human subjects.Methods: This was a double-blind, placebo controlled, crossover study. Participants were randomized to receive either two capsules of Withania somnifera extract 250 mg or two capsules of placebo twice daily for 14 days. Pharmacodynamic parameters heart rate, aortic pressure, augmentation index (AIx), subendocardial viability ratio (SEVR), radial and aortic blood pressure (BP) were recorded before and after CPT at baseline and at end of treatment. After washout period of 10 days, subjects crossed over to other treatment group and same procedure was repeated. Safety assessments were done at baseline and at end of treatment.Results: A total of 20 volunteers completed the study. Compared with baseline and placebo, Withania somnifera extract produced a significant decrease in mean percent change of arterial stiffness indices (AIx, radial and aortic BP). SEVR with CPT increased, however it was non-significant compared to baseline and placebo. Both treatments were well-tolerated and no serious adverse events were reported.Conclusions: Withania somnifera extract showed a significant decrease in cold pressor stress test induced changes on aortic wave reflections, suggesting its beneficial effects in reducing stress induced cardiovascular changes. However, further clinical studies are warranted to evaluate these effects in patients with cardiovascular and other associated diseases

EVALUATION OF CARDIOVASCULAR AND PHARMACODYNAMIC EFFECTS OF TERMINALIA ARJUNA SINGLE DOSE AND MULTIPLE DOSE IN HEALTHY HUMAN MALES

Context: Terminalia arjuna is a medicinal plant used as a cardiotonic in Ayurveda. The presence of potent antioxidant constituents results in improvement in endothelial dysfunction seen in coronary artery disease.Aim: To evaluate the cardiovascular and pharmacodynamic effects of single and multiple doses of Terminalia arjuna in healthy human male subjects.Settings and Design: Randomized, double blind, placebo-controlled dose ranging study.Methods and Material: After approval from the institutional ethics committee, written informed consent was taken from subjects. Eligible subjects were allocated to the single and multiple dose groups, with six subjects in each group. The active treatment (Terminalia arjuna crude powder capsules of 500 mg, 1000 mg, 1500 mg &amp; 2000 mg single dose and 1500 mg multiple dose) and placebo capsules were administered in 2:1 ratio in all the study groups. Vital parameters and pharmacodynamic assessment of cardiac profiling were performed using cold pressor test (CPT), tilt table and platelet aggregation tests.Statistical analysis used: The data was presented as mean ±SD. No statistical tests were applied as the sample size was less (n=6 in each group).Results: During CPT, Terminalia arjuna attenuated the rise in SBP, DBP and pulse rate in all the treatment groups compared to baseline. The CPT induced arterial stiffness was counteracted by treatment with 1500 mg &amp; 2000 mg single dose and 1500 mg multiple doses of Terminalia arjuna. Cardiac output was increased with 1500 mg multiple dose at 600 tilt (Day 1) and at 450 &amp; 600 phases of the tilt (Day 11). Platelet aggregation was markedly inhibited in 1500 mg multiple doses at Day 11.Conclusions: Treatment with single (1500 mg &amp; 2000 mg) and multiple doses (1500 mg for 10 days) of Terminalia arjuna produced remarkable changes in the cardiovascular profile. Further studies in larger number of subjects and in patients with cardiovascular diseases are needed to confirm these effects

EVALUATION OF A HIGHLY STANDARDIZED WITHANIA SOMNIFERA EXTRACT ON ENDOTHELIAL DYSFUNCTION AND BIOMARKERS OF OXIDATIVE STRESS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED STUDY

Background: Type 2 Diabetes mellitus is a multisystem disorder with oxidative stress and endothelial dysfunction. Withania somnifera Dunal (Ashwagandha) is shown to have potent antioxidant, hypoglycemic and hypolipidemic effects in several studies. The present study was planned to compare the effect of Withania somnifera on endothelial dysfunction and biomarkers in patients with diabetes mellitus. Materials and Methods: After taking IEC approval and written informed consent, 66 eligible patients, who are on metformin therapy, were randomized to receive either one capsule of highly standardized aqueous extract of Withania somnifera 250mg twice daily, one capsule of Withania somnifera 500mg twice daily or Placebo for a duration of 12 weeks. Primary efficacy parameter was a change in endothelial function (measured as change in reflection index of more than 6 %) performed by salbutamol challenge test at baseline and after 12 weeks of treatment. Secondary end points were change in biomarkers of oxidative stress (malondialdehyde, nitric oxide and glutathione), high sensitivity C-reactive protein and change in lipid profile. Safety lab parameters were measured, at baseline and after 12 weeks of treatment. Results: A total of 60 patients completed the study. Twelve weeks of treatment with Withania somnifera 250mg and 500mg produced significant reduction in reflection index (-2.52±1.32% to -7.49±3.49%) and (-2.24±1.00% to -9.03±2.42%) respectively, suggesting improvement in endothelial function versus placebo (-2.11±1.62% to -0.81±2.86%). Similarly a significant improvement in biomarkers of oxidative stress, systemic inflammation, lipid parameters and HbA1c levels, compared to baseline and placebo, was observed with Withania somnifera. All treatments are well tolerated. Conclusion: Withania somnifera showed significant improvement in endothelial function, reduction in biomarkers of oxidative stress and systemic inflammation and can be used as a therapeutic adjunctive in patients with type 2 Diabetes mellitus

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP CLINICAL STUDY TO EVALUATE THE ANALGESIC EFFECT OF AQUEOUS EXTRACT OF TERMINALIA CHEBULA, A PROPRIETARY CHROMIUM COMPLEX, AND THEIR COMBINATION IN SUBJECTS WITH JOINT DISCOMFORT

Objective: To evaluate the analgesic effect of an aqueous extract of Terminalia chebula (TCE), a proprietary chromium complex (PCC), and theircombination in subjects with joint discomfort.Methods: A total of 100 patients with knee joint discomfort were randomized into five treatment groups - TCE 500 mg BID, TCE 500 mg BID+PCC400 µg OD, PCC 400 µg OD alone, placebo, and TCE 250 mg BID, for 12 weeks in a double-blinded manner. Assessment of symptoms of knee joint painand discomfort was done by modified Western Ontario and McMaster Universities Arthritis Index (mWOMAC) and knee swelling index (KSI); visualanalog scale (VAS) was used for subjective assessment of pain, stiffness, and disability. Statistical analysis was done with GraphPad Prism 6.Results: Absolute reduction in mWOMAC score in TCE 500 mg (19.82±8.35), TCE 500 mg+PCC 400 µg (13.10±5.69), PCC 400 µg (8.30±3.81), placebo(2.45±3.07), and TCE 250 mg (10.47±4.43), respectively, at the end of 12 weeks as compared to the baseline values. Absolute reduction in KSI inTCE 500 mg (28.95±16.82), TCE 500 mg+PCC 400 µg (19.14±9.50), PCC 400 µg (12.7±4.86), placebo (10.03±3.8), and TCE 250 mg (18.24±6.86),respectively, at the end of 12 weeks as compared to the baseline values (p&lt;0.001). Similar results were seen with VAS assessments for pain, stiffness,and disability. All the treatments were well tolerated.Conclusion: TCE and PCC reduce joint discomfort.Keywords: Terminalia chebula extract, Proprietary chromium complex, Western Ontario and McMaster Universities Arthritis Index

Pirfenidone Induced Photosensitivity Reaction in a Patient with Idiopathic Pulmonary Fibrosis

Drug-induced photosensitivity refers to the development of cutaneous disease as a result of combined effects of a chemical and light. Photosensitivity reactions may result from systemic medications and topically applied compounds. Pirfenidone is known to cause photosensitivity reactions, rash, pruritus and dry skin at high doses. However, similar adverse reactions with low doses of Pirfenidone have not been reported. We report a case of photosensitivity reaction induced by low- dose Pirfenidone in a patient with idiopathic pulmonary fibrosis (IPF)

A randomized, double-blind, placebo-controlled, cross-over study to evaluate analgesic activity of Terminalia chebula in healthy human volunteers using a mechanical pain model

Background and Aims: To evaluate analgesic activity and safety of single oral dose (1000 mg) of Terminalia chebula using a mechanical pain model in healthy human volunteers. Material and Methods: Twelve healthy volunteers were randomized to receive either single oral dose of 2 capsules of T. chebula 500 mg each or identical placebo capsules in a double-blinded manner. Mechanical pain was assessed using Ugo basile analgesy meter (Randall–Selitto test) before and 3 h after administration of test drug. The parameters evaluated were pain threshold force and time; pain tolerance force and time. A washout period of 1-week was given for crossover between active drug and placebo. Results: Terminalia chebula significantly increased the mean percentage change for pain threshold force and time, and pain tolerance force and time compared to placebo (P < 0.001). The mean percentage change for pain threshold force and time (20.8% and 21.0%) was increased more than that of pain tolerance force and time (13.4% and 13.4%). No adverse drug reaction was reported with either of the study medications during the study period. Conclusion: T. chebula significantly increased pain threshold and pain tolerance compared to placebo. Both the study medications were well tolerated. Further multiple dose studies may be needed to establish the analgesic efficacy of the drug in patients suffering from osteoarthritis, rheumatoid arthritis and other painful conditions

Evaluation of effect of highly standardized aqueous extract of roots and leaves of Withania somnifera on cold pressor test induced cardiovascular changes in healthy human subjects

Background: Stress is an important cardiovascular risk factor. Cold pressor test (CPT) is a simple, validated, non-invasive test used to measure stress induced changes in cardiovascular parameters. The objective of this study was to evaluate effect of Withania somnifera extract on cold pressor stress test induced changes on cardiovascular parameters and aortic wave reflections in healthy human subjects.Methods: This was a double-blind, placebo controlled, crossover study. Participants were randomized to receive either two capsules of Withania somnifera extract 250 mg or two capsules of placebo twice daily for 14 days. Pharmacodynamic parameters heart rate, aortic pressure, augmentation index (AIx), subendocardial viability ratio (SEVR), radial and aortic blood pressure (BP) were recorded before and after CPT at baseline and at end of treatment. After washout period of 10 days, subjects crossed over to other treatment group and same procedure was repeated. Safety assessments were done at baseline and at end of treatment.Results: A total of 20 volunteers completed the study. Compared with baseline and placebo, Withania somnifera extract produced a significant decrease in mean percent change of arterial stiffness indices (AIx, radial and aortic BP). SEVR with CPT increased, however it was non-significant compared to baseline and placebo. Both treatments were well-tolerated and no serious adverse events were reported.Conclusions: Withania somnifera extract showed a significant decrease in cold pressor stress test induced changes on aortic wave reflections, suggesting its beneficial effects in reducing stress induced cardiovascular changes. However, further clinical studies are warranted to evaluate these effects in patients with cardiovascular and other associated diseases