The Phosphodiesterase 5 Inhibitor Sildenafil as an Adjunct to Antidepressants in Major Depressive Disorder Patients

Sponsor

Sadat City University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04344678

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Antidepressant-like effects of sildenafil to its ability to modulate transduction pathways responsible for neuroplasticity. Treatment with sildenafil was shown to be PKG-dependent and lead to increased expression of cGMP, pCREB, BDNF and VGF in the hippocampus and prefrontal cortex (PFC), brain areas relevant to mood disorders pathophysiology. Sildenafil produces antidepressant-like effects by inhibiting oxidative stress in the hippocampus and by decreasing the levels of IL-1β in the hippocampus and striatum.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Sildenafil Citrate Drug: Placebo oral tablet	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

The Phosphodiesterase 5 Inhibitor Sildenafil as an Adjunct to Antidepressants in Major Depressive Disorder Patients: Randomized, Double-Blind, Placebo-Controlled Trial

Actual Study Start Date :

Jan 1, 2020

Anticipated Primary Completion Date :

Oct 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control group Escitalopram 20 mg tablet plus one placebo tablet	Drug: Placebo oral tablet Esitalopram 20 mg tablet plus placebo tablet once daily
Experimental: Sildenafil group Escitalopram 20 mg tablet plus one Sildenafil 50 mg tablet	Drug: Sildenafil Citrate Esitalopram 20 mg tablet plus Sildenafil Citrate 50 mg tablet once daily

Arm

Intervention/Treatment

Placebo Comparator: Control group

Escitalopram 20 mg tablet plus one placebo tablet

Drug: Placebo oral tablet

Esitalopram 20 mg tablet plus placebo tablet once daily

Experimental: Sildenafil group

Escitalopram 20 mg tablet plus one Sildenafil 50 mg tablet

Drug: Sildenafil Citrate

Esitalopram 20 mg tablet plus Sildenafil Citrate 50 mg tablet once daily

Outcome Measures

Primary Outcome Measures

Effect on Hamilton Depression rating scale score (HAM-D score) [12 week]
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.

Secondary Outcome Measures

Effect on biological markers [12 week]
Serum level of tumor necrosis factor alpha (TNF-α), Interleukin-6 (IL-6), and brain derived neurotrophic factor (BDNF) were measured at the baseline and after the treatment to evaluate the biological effects of the used medications.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Faculty of Medicine	Shibīn Al Kawm		Egypt

Sponsors and Collaborators

Sadat City University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Mahmoud Samy Abdallah, Lecturer of Clinical Pharmacy, PhD., Sadat City University

ClinicalTrials.gov Identifier:

NCT04344678

Other Study ID Numbers:

0044/2020

First Posted:

Apr 14, 2020

Last Update Posted:

Jan 20, 2022

Last Verified:

Jan 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Depressive Disorder

Depression

Depressive Disorder, Major

Sildenafil Citrate

Study Results

No Results Posted as of Jan 20, 2022