The DPP-4 Inhibitor Vildagliptin as Adjunct in Major Depressive Disorder Patients

Study Overview
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Brief Summary
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Vildagliptin, an antidiabetic drug that inhibits the dipeptidyl peptidase- 4 (DPP-4), increases glucagon-like peptide-1 (GLP-1) and regulates blood glucose levels, favoring weight loss and lowering cardiovascular risk. A retrospective longitudinal study by Rizzo et al. showed that DPP-4 inhibitors administration could have protective effects against cognitive decline in diabetic elderly. Is has been observed that GLP-1 affects brain metabolism, increases neuritic growth, and protects neuronal cells from oxidative stress and death.

Official Title
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The DPP-4 Inhibitor Vildagliptin as Adjunct in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Vildagliptin 50 MG
* Drug: Escitalopram 20 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighty adult outpatients with the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of MDD based on a MINI Neuropsychiatric Interview (MINI) (American Psychiatric Association., 2000; Sheehan et al., 1998), without psychotic features and a total 17 item HAM-D score of at least 18 with item 1 (depressed mood) scored 2 or greater were eligible (Hamilton, 1960). Patients were requested to be free of all the psychotropic and anti-inflammatory medications for at least 4 weeks before participating in the study. Exclusion Criteria: Patients with bipolar I or bipolar II disorder Patients with personality disorders Patients with eating disorders Patients with substance dependence or abuse Patients with concurrent active medical condition Patients with history of seizures Patients with history of receiving Electroconvulsive therapy (ECT) Patients with inflammatory disorders Patients with allergy or contraindications to the used medications Patients with finally pregnant or lactating females Cardiovascular disorders Severe renal impairment: creatinine clearance of ≤ 25 ml/min Moderate or severe hepatic impairment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>Escitalopram 20 mg tablet once daily for 12 week plus placebo tablet once daily for 12 weeks | Drug: Escitalopram 20 mg<br>* Escitalopram,Selective serotonin reuptake inhibitor- Cilostazol, a selective phosphodiesterase 3 (PDE3) inhibitor, acts as an antiplatelet agent and has been widely approved for treatment of intermittent claudication with peripheral arterial disease and for secondary prevention of ischemic stroke.<br>|
| Experimental: Vildagliptin group<br>Escitalopram 20 mg tablet once daily for 12 week plus Vildagliptin 50mg tablet once daily for 12 weeks | Drug: Vildagliptin 50 MG<br>* Vildagliptin, an antidiabetic drug that inhibits the dipeptidyl peptidase- 4 (DPP-4), increases glucagon-like peptide-1 (GLP-1) and regulates blood glucose levels, favoring weight loss and lowering cardiovascular risk.<br>Drug: Escitalopram 20 mg<br>* Escitalopram,Selective serotonin reuptake inhibitor- Cilostazol, a selective phosphodiesterase 3 (PDE3) inhibitor, acts as an antiplatelet agent and has been widely approved for treatment of intermittent claudication with peripheral arterial disease and for secondary prevention of ischemic stroke.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on Hamilton Depression rating scale score (HAM-D score) | 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. | 12 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on biological markers | Serum level of tumor necrosis factor alpha (TNF-α) | Baseline and 12 week | 
| Interleukin-6 | Serum level of Interleukin-6 (IL-6) | Baseline and 12 week | 
| BDNF | Serum level of Brain derived neurotrophic factor (BDNF) | Baseline and 12 week |