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

Phase 1

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: Placebo; Drug: Roflumilast 500Mcg Tab

• Registration Number: NCT04751071
• Lead Sponsor: Sadat City University

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2021-02-01
• Study First Submitted: 2021-02-03
• Study First Submitted QC: 2021-02-10
• Study First Posted: 2021-02-11
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-21
• Primary Completion: 2024-10-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	placebo tablet plus standard therapy
Roflumilast	Roflumilast 500Mcg Tab	Roflumilast 500 µg tablet plus standard therapy

Primary Outcome Measures

Name	Time	Method
Effect on Hamilton Depression rating scale score (HAM-D score)	6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Effect on biological markers	6 weeks	Serum level of Nuclear factor kappa

Trial Locations

Locations (1)

Faculty of Pharmacy; 🇪🇬 Shibeen Elkom, Menoufia, Egypt