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Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

ABSTRACT: Background: Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death. In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic in vitro and in a retrospective observational study of adult dengue patients with type 2 diabetes. This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity. Methods: This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events. Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients. Discussion: Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses. Trial registration: ClinicalTrials.gov: NCT04377451 (May 6 ^th 2020).

SUBMITTER: Nguyen NM

PROVIDER: S-EPMC7539082 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

Nguyen Nguyet Minh NM Nguyen Nguyet Minh NM Chanh Ho Quang HQ Tam Dong Thi Hoai DTH Vuong Nguyen Lam NL Chau Nguyen Thi Xuan NTX Chau Nguyen Van Vinh NVV Phong Nguyen Thanh NT Trieu Huynh Trung HT Luong Thi Hue Tai T Cao Thi Tam T Dinh The Trung T Duyen Huynh Thi Le HTL Van Ninh Thi Thanh NTT Nguyen Than Ha Quyen Q Rivino Laura L Gallagher Peter P Jones Nick K NK Geskus Ronald B RB Kestelyn Evelyne E Yacoub Sophie S

Wellcome open research 20200101

<b>Background:</b> Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death. In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, li ...[more]

PMID: 33083561

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Project description:Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90-120 mg/dL (5.0-6.7 mmol/L). Pubertal maturation was determined by Tanner stage.Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short-acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups.This 9-month RCT of adjunctive metformin therapy in overweight and obese youth with T1D resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group.ClinicalTrial.gov NCT01334125.

Project description:ObjectivePolyethylene glycol loxenatide (PEG-Loxe) is a novel, once-weekly glucagon-like peptide 1 receptor agonist that is approved in doses of 0.1 mg and 0.2 mg for the treatment of type 2 diabetes mellitus (T2DM). However, no clinical trials have been designed to determine the effect of 0.3 mg PEG-Loxe on weight loss in overweight or obese patients with T2DM. This trial aimed to evaluate the short-term effect of 0.3 mg PEG-Loxe, injected subcutaneously once weekly, for weight management in overweight or obese patients with T2DM.MethodsThis 16-week, open-label, parallel-arm, randomized, metformin-controlled trial was conducted at Shandong Provincial Hospital in Shandong, China. Patients with T2DM, who were overweight or obese (body mass index ≥ 25.0 kg/m2) and had been treated with lifestyle interventions or a combination with oral antidiabetic drug monotherapy were randomized (2:1) to receive 0.3 mg PEG-Loxe or 1500 mg metformin. The primary endpoint was a change in body weight from baseline to week 16.ResultsOverall, 156 patients were randomized and exposed to treatment. Weight loss was 7.52 kg (8.37%) with PEG-Loxe and 2.96 kg (3.00%) with metformin, with a between-group difference of 4.55 kg (95% CI, 3.43 to 5.67) (P < 0.001). A significantly higher proportion of patients lost ≥5% (61.5% vs. 25.0%) or 10% (26.9% vs. 5.8%) body weight in the PEG-Loxe group than in the metformin group (P < 0.01). Additionally, PEG-Loxe resulted in marked improvements in several cardiovascular risk factors compared to metformin, including body mass index, waist circumference, visceral fat area, blood pressure, and lipid profile. PEG-Loxe and metformin displayed almost equal potency for glycemic control. The incidence of adverse events was 46.2% (48/104) and 44.2% (23/52) in the PEG-Loxe and metformin groups, respectively.ConclusionIn overweight or obese patients with T2DM, a once-weekly subcutaneous administration of PEG-Loxe for 16 weeks, in addition to lifestyle interventions or oral antidiabetic drug therapy, resulted in significantly greater weight loss compared to metformin. Additional trials are necessary to establish whether these effects can be maintained in the long term.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2200057800.

Project description:ObjectivesCanagliflozin (CANA), a kind of sodium-glucose cotransporter-2 (SGLT-2) inhibition, study in which the role of CANA monotherapy in polycystic ovary syndrome (PCOS) has been investigated, and it could become a novel option in the PCOS treatment. Nevertheless, trials focused on SGLT-2 combination therapy's efficacy, and safety in PCOS patients are limited. This randomized controlled trial compared the efficacy and safety of CANA and metformin (MET) combination therapy and MET monotherapy in endocrine and metabolic profiles of overweight and obese women with polycystic ovary syndrome (PCOS).MethodsFifty-one overweight or obese non-diabetic PCOS women between 18 and 40 years old were enrolled. Patients were randomly allocated to receive either CANA/MET or MET treatment. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily, while the MET group received MET 1000 mg twice daily for three months. Changes in menstrual pattern, anthropometric parameters, gonadal parameters, glucose and lipid homeostasis, and adverse events (AEs) were evaluated.ResultsCompared with the MET group, women have a significantly lower level of total testosterone (TT), area under the curve for glucose (AUCGlu), and area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group. There were no significant differences in menstrual frequency, body weight, body mass index, follicle-stimulating hormone, luteinizing hormone, free androgen index, sex hormone-binding globulin, androstenedione, fasting blood glucose, fasting insulin, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio. AEs were seen in 57.70% (15/26) and 68.00% (17/25) of patients in the CANA/MET and MET groups, respectively.ConclusionsIn overweight and obese women with PCOS, CANA and MET combination therapy may be similar to MET monotherapy in improving menstrual frequency, weight control, hyperandrogenemia, and relieving insulin resistance. CANA/MET may have more benefits in reducing TT, AUCGlu, and the AUCIns/AUCGlu ratio within three months than MET monotherapy.Trial registrationClinicalTrials.gov, NCT04973891.

Project description:OBJECTIVE:The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. METHODS:One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. RESULTS:One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. CONCLUSIONS:Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia. TRIAL REGISTRATION:chictr.org ChiCTR-IOR-15006278.

Dataset Information

Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

Publications

Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

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