Efficacy of Metformin With Antidepressant Medication as Adjunct Therapy in Depression-obesity Ccomorbidity and Ssociation With NEGR1/RPL31P12 Variants Based on Genotyping
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Change in Severity of the depression
研究概览
简要总结
The patients with depression and obesity will receive add-on metformin with antidepressant therapy, which may result in greater improvement in depressive symptoms and BMI reduction compared to antidepressant monotherapy. NEGR1/RPL31P12 gene polymorphisms may influence the comparative efficacy of antidepressant monotherapy versus combination therapy (antidepressant + metformin) in Pakistani patients. Patients with certain variants may respond better or worse to antidepressants and may have different weight outcomes.
详细描述
There is a substantial percentage of the Pakistani population who are both overweight/obese and depressed, with estimates from clinical samples averaging 25%. So, the personalized treatment approach for depression and obesity needs to be explored.
Obesity and depression commonly coexist and are associated with poorer health outcomes. Metformin, widely used for metabolic disorders and obesity, has shown potential antidepressant effects. However, evidence on its use as an adjunct to antidepressant therapy in patients with depression-obesity comorbidity remains limited, and the influence of genetic variants on treatment response is not well understood. This study aims to evaluate the effectiveness of adjunctive metformin and its association with NEGR1 and RPL31P12 genetic variants in this population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group I: Normal Controls Group II: Depression Group III: Obesity
- •Group IV and V:
- •Age ≥ 18 years
- •Both males and females
- •Recurrent depressive disorder (6A71) according to ICD-11,
- •Asian cut off: Obese and overweight (BMI < 23)
- •BDI score ≥ 13 or PHQ score ≥ 4
- •Either medication-naïve or medication-free for at least 2 weeks before enrollment, or the patient did not take antidepressants during the last 7 days before study entry (discontinuation of effective medication to enable study participation is prohibited)
- •In case of non-psychotropic medication: The patient received stable pharmacological medication for at least 14 days before study entry (any changes in medication dose or frequency of therapy must be answered with no)
排除标准
- •Groups I-III: Negative Controls (Normal: no depression and Obesity for SNP comparison only)
- •Age less than 18
- •Dementia/ Mentally impaired who can not fill self report performas for inclusion criteria
- •Group IV: Positive Control (RCT patients)
- •Patients with comorbid conditions (HTN, CKD) if taking any drug for that condition.
- •The patient is not an employee of the investigator study site, or a family member of the employees or the investigator, or otherwise dependent on the sponsor, the investigator, or the investigator study site.
- •The patient did not participate in other interventional trials during the 6 months before and at the time of this trial. The patient does not have a history of non-response to antidepressants included in the study.
- •The patient has not given birth within the 6 months before study entry and is not breastfeeding
- •The patient did not receive treatment with ketamine, irreversible MAO inhibitor (e.g. tranylcypromine), electroconvulsive therapy (ECT) or other stimulatory treatments in the index episode.
- •The patient is not diagnosed with dementia and does not have moderate or severe impairment of general cognitive function according to clinical impression.
- •The patient does not meet the criteria for alcohol use disorder (DSM-5: 303.90; ICD-10: F10.20) or substance use disorder (DSM-5: 304; ICD-10: F11.20 - F19.20) in DSM-5, and a urine/serum drug screening is negative (except for benzodiazepines and opiates).
- •The patient does not have:
- •A known allergy or contraindication against antidepressants included in the study
- •History of suicidal tendencies
- •Uncontrolled hepatic disorder, renal or cardiovascular disease
- •Untreated hypothyroidism
- •History of myocardial infarction or stroke
- •Symptomatic peripheral arterial disease
- •Monogenic familial hypercholesterolemia
研究组 & 干预措施
Adjunctive Metformin Therapy
Tab Sertraline 50 mg/day + Metformin or Cap Duloxetine 60 mg/day + Metformin or Tab Bupropion XL 150-300 mg/day + Metformin
干预措施: Metformin (Drug)
Antidepressant Monotherapy
Tab Sertraline 50 mg/day or Cap Duloxetine 60 mg/day or Tab Bupropion XL 150-300 mg/day
干预措施: Antidepressant Therapy (Drug)
Adjunctive Metformin Therapy
Tab Sertraline 50 mg/day + Metformin or Cap Duloxetine 60 mg/day + Metformin or Tab Bupropion XL 150-300 mg/day + Metformin
干预措施: Antidepressant Therapy (Drug)
结局指标
主要结局
Change in Severity of the depression
时间窗: 1 month
The change in the total PHQ-9 score between baseline and 4-weeks follow-up is the primary outcome measure. This measure is a patient-rated inventory of depressive symptoms. All items are scored on scales ranging from 0-3 and the sum of the scores provides the total score for the measure. On this scale, higher scores indicate poorer outcomes. Scores 9-19 and 20-27 are considered moderate and severe depression respectively.
Change in BMI
时间窗: 3 months
Change in Body Mass Index (BMI): BMI will be measured at baseline and study completion and calculated as weight in kilograms divided by height in meters squared (kg/m²). The outcome will be assessed as the change in BMI from baseline. Asian BMI Classification: Underweight: \< 18.5 kg/m² Normal weight: 18.5-22.9 kg/m² Overweight: 23.0-24.9 kg/m² Obesity Class I: 25.0-29.9 kg/m² Obesity Class II: ≥ 30.0 kg/m² BMI reduction \< 1 kg/m²: Minimal change BMI reduction ≥ 1 kg/m²: Clinically meaningful improvement Weight loss ≥ 5% of baseline body weight: Clinically significant weight reduction associated with metabolic health benefits. A decrease in BMI from baseline and/or movement to a lower BMI category will be considered indicative of improvement in obesity-related outcomes.
次要结局
- Change in Blood Pressure(3 months)
- Change in Blood Sugar Levels(3 months)
- Change in Renal Function tests(3 months)
- Change in Liver Function tests(3 months)
- C - Reactive Proteins levels(3 months)
- Lipid Profile(3 months)
研究者
Afifa Siddique
Assistant Professor
Riphah International University