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

Sponsor

Sadat City University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04751071

Collaborator

(none)

Enrollment

Location

Arms

21.9

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Roflumilast 250Mcg Tab Drug: Placebo	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Roflumilast Roflumilast 250 µg tablet plus standard therapy	Drug: Roflumilast 250Mcg Tab Roflumilast 250 µg tablet once daily for 6 weeks plus the standard therapy
Placebo Comparator: Placebo placebo tablet plus standard therapy	Drug: Placebo Placebo tablet once daily for 6 weeks plus the standard therapy

Arm

Intervention/Treatment

Active Comparator: Roflumilast

Roflumilast 250 µg tablet plus standard therapy

Drug: Roflumilast 250Mcg Tab

Roflumilast 250 µg tablet once daily for 6 weeks plus the standard therapy

Placebo Comparator: Placebo

placebo tablet plus standard therapy

Drug: Placebo

Placebo tablet once daily for 6 weeks plus the standard therapy

Outcome Measures

Primary Outcome Measures

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

Effect on biological markers [6 weeks]
Serum level of brain derived neurotrophic factor (BDNF)
Effect on biological markers [6 weeks]
Serum level of cAMP response element-binding protein (CREB)
Effect on biological markers [6 weeks]
Serum level of SEROTONIN
Effect on biological markers [6 weeks]
Serum level of tumor necrosis factor alpha (TNF-α)
Effect on biological markers [6 weeks]
Serum level of Interleukin-6 (IL-6)
Effect on biological markers [6 weeks]
Serum level of Nuclear factor kappa

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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Faculty of Pharmacy	Shibeen Elkom	Menoufia	Egypt	13829

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, Sadat City University

ClinicalTrials.gov Identifier:

NCT04751071

Other Study ID Numbers:

NS10/2021

First Posted:

Feb 11, 2021

Last Update Posted:

Feb 22, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

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

Study Results

No Results Posted as of Feb 22, 2022