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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Escitalopram 20 mg; Drug: Vildagliptin 50 MG

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Mahmoud S Abdallah; Phone Number: 00201063340887; Email: Mahmoud.samy@fop.usc.edu.eg

Study Locations

• Egypt
  • Shibīn Al Kawm, Egypt
    • Faculty of medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Escitalopram 20 mg tablet once daily for 12 week plus placebo tablet once daily for 12 weeks	Drug: Escitalopram 20 mg; 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.
Experimental: Vildagliptin group; Escitalopram 20 mg tablet once daily for 12 week plus Vildagliptin 50mg tablet once daily for 12 weeks	Drug: Escitalopram 20 mg; 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.; Drug: Vildagliptin 50 MG; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sadat City University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 1, 2020

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dipeptidyl-Peptidase IV Inhibitors; Selective Serotonin Reuptake Inhibitors; Vildagliptin; Escitalopram
• Other Study ID Numbers: 0055/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No