The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients
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|ClinicalTrials.gov Identifier: NCT04088448|
Recruitment Status : Recruiting
First Posted : September 12, 2019
Last Update Posted : September 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder||Drug: Placebo oral tablet Drug: Metformin||Phase 1 Phase 2|
Selective Serotonin Reuptake Inhibitors (SSRIs) represent the standard treatment for Major Depressive Disorder (MDD). However, their efficacy is variable and incomplete. In order to explain, at least in part, such variable efficacy, we have shown that SSRI administration does not affect mood per se but, by enhancing neural plasticity, amplifies the influence of the living conditions on mood. Consequently, in a favorable environment, SSRI treatment leads to a reduction of symptoms while, in stressful conditions, it could lead to a worse prognosis. Here, we test the hypothesis that, given the clear association between living conditions and metabolic profile, the modulation of the latter may mimic the effect of the environment on SSRI outcome, determining treatment efficacy.
Metformin is widely used as a first line treatment for patients with type 2 diabetes mellitus for more than 60 years for the reduction of hepatic glucose output and increase of the insulin mediated utilization of glucose. Previous studies demonstrated that metformin can rapidly cross the blood brain barrier and has several beneficial effects in the brain such as anti-inflammatory and neuroprotective effects. Furthermore, metformin, along with its anti-glycemic effects, has been documented to possess anti-depression effects in patients with type 2 diabetes. In Guo's study, 58 participants diagnosed with depression and type 2 diabetes were divided into two groups: one treated with metformin and the other with a placebo for 24 weeks. Analysis of MADRS and HRSD-17 scores showed that metformin significantly reduced MADRS scores and HRSD-17 scores. Metformin administration improves depressive symptoms in type 2 diabetes mellitus.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||The Antidiabetic Metformin as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial|
|Actual Study Start Date :||January 1, 2019|
|Estimated Primary Completion Date :||January 31, 2020|
|Estimated Study Completion Date :||June 30, 2020|
Placebo Comparator: Control group
Fluoxetine 20 mg capsule once daily for 12 week plus placebo tablet once daily for 12 weeks
Drug: Placebo oral tablet
Fluoxetine 20 mg capsule plus Placebo tablet administered once daily after food
Experimental: Metformin group
Fluoxetine 20 mg capsule once daily for 12 week plus Metformin 1000 mg XR tablet once daily for 12 weeks
Fluoxetine 20 mg capsule plus Metformin 1000 mg extended release tablet administered once daily after food
- Effect on Hamilton Depression rating scale score (HAM-D score) [ Time Frame: Baseline to week 12 ]The principal measure of the outcome was the 17-items HAM-D. Scoring is based on the 17-item scale and scores of 0-7 are considered as being normal, 8-13 suggest mild depression, 14-17 moderate depression and scores over 17 are indicative of severe depression. Remission is defined as HAM-D total score ≤ 7 (primary outcome). Treatment response is defined as ≥ 50% drop in the HAM-D total score.
- Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 12 [ Time Frame: Baseline to week 12 ]The MADRS is a clinician-rated scale for assessing depressive symptomatology that had occurred in participants during the week preceding each interview. Patients were rated on 10 items to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores on the 10 items and ranged from 0 to 60. A higher score indicated more depressive symptomatology. A negative change score indicated improvement.
- TNF-α [ Time Frame: Baseline to week 12 ]Serum level of tumor necrosis factor alpha (TNF-α)
- BDNF [ Time Frame: Baseline to week 12 ]Serum level of brain derived neurotrophic factor (BDNF),
- CRP [ Time Frame: Baseline to week 12 ]Serum level of C-Reactive Protein
- IGF‑1 [ Time Frame: Baseline to week 12 ]Serum level of Insulin-Like Growth Factor
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04088448
|Contact: Mahmoud S Abdallah||00201063340887||Mahmoud.email@example.com|
|Faculty of Medicine||Recruiting|
|Contact: Mahmoud S Abdallah, PhD|