The Phosphodiesterase 4 Inhibitor Roflumilast as an Adjunct to Antidepressants in Major Depressive Disorder Patients

Major Depressive Disorder Clinical Trial

Official title:

The Phosphodiesterase 4 Inhibitor Roflumilast as an Adjunct to Antidepressants in Major Depressive Disorder Patients. Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04751071
• Other study ID #: 10/2021NEUR2
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 1, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: November 2023
• Source: Sadat City University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

n pre-clinical studies and early-stage clinical trials, PDE4 inhibitors such as rolipram have been shown to enhance memory. They also improve depressive-like behaviors induced by chronic unpredictable mild stress, lipopolysaccharide, or ethanol abstinence . Consequently, it is reasonable to believe that PDE4 is a potential target for treatment of the comorbidity of depression and AD.The aim of the current study is to evaluate the potential adjunct antidepressant effect of the Phosphodiesterase-4 Inhibitor Roflumilast in adult patients with MDD.

Description:

Phosphodiesterase-4 (PDE4), an important member of the PDE superfamily, is a key regulator of intracellular cyclic AMP (cAMP) level. As the second messenger, cAMP activates protein kinase A, which phosphorylates the subsequent downstream cAMP-response element binding (CREB) protein. In the central nervous system, this signaling cascade exerts both pre- and post-synaptic effects and is essential for a variety of cellular functions, including neurotransmitter release and neuroprotection. Inhibition of PDE4 prevents cAMP breakdown, which is well recognized as the mechanism by which PDE4 inhibitors can treat impaired memory linked to several brain disorders. In pre-clinical studies and early-stage clinical trials, PDE4 inhibitors such as rolipram have been shown to enhance memory. They also improve depressive-like behaviors induced by chronic unpredictable mild stress, lipopolysaccharide, or ethanol abstinence . Consequently, it is reasonable to believe that PDE4 is a potential target for treatment of the comorbidity of depression and AD.

The aim of the current study is to evaluate the potential adjunct antidepressant effect of Roflumilast in adult patients with MDD. Furthermore, we will assess the relationship between HAM-D score and BDNF as well as their role as a therapeutic targets of MDD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 1, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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 20 with item 1 (depressed mood) scored 2 or greater were eligible (Hamilton, 1960).

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Roflumilast 500Mcg Tab
Roflumilast 500µg tablet once daily for 6 weeks plus the standard therapy
• Placebo
Placebo tablet once daily for 6 weeks plus the standard therapy

Locations

Country	Name	City	State
Egypt	Faculty of Pharmacy	Shibeen Elkom	Menoufia

Sponsors (1)

Lead Sponsor	Collaborator
Sadat City University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect on Hamilton Depression rating scale score (HAM-D score)	The principal measure of the outcome was the 17-items Effect on Hamilton Depression rating scale score. 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 Effect on Hamilton Depression rating scale total score = 7 (primary outcome). Treatment response is defined as = 50% drop in the Effect on Hamilton Depression rating scale total score.	6 weeks
Secondary	Effect on biological markers	Serum level of brain derived neurotrophic factor (BDNF)	6 weeks
Secondary	Effect on biological markers	Serum level of cAMP response element-binding protein (CREB)	6 weeks
Secondary	Effect on biological markers	Serum level of SEROTONIN	6 weeks
Secondary	Effect on biological markers	Serum level of tumor necrosis factor alpha (TNF-a)	6 weeks
Secondary	Effect on biological markers	Serum level of Interleukin-6 (IL-6)	6 weeks
Secondary	Effect on biological markers	Serum level of Nuclear factor kappa	6 weeks