Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression

Depression Clinical Trial

— REGAIN  

Official title:

A 21-week, Multicenter, Open Label Study to Evaluate the Safety and Tolerability Profile of the Combination of a SSRI or SNRI Antidepressive Therapy With Oral Fingolimod in the Treatment of RRMS Patients With Mild to Moderate Depression

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01436643
• Other study ID #: CFTY720DDE06
• Secondary ID: 2011-001692-39
• Status: Terminated
• Phase: Phase 4
• First received: September 16, 2011
• Last updated: September 24, 2014
• Start date: November 2011
• Est. completion date: September 2013

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

This is a prospective, multi-center, open-label study in Relapsing-remitting Multiple Sclerosis (RRMS) patients with mild to moderate depression treated with selected serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI) antidepressants over 16 weeks as add-on to fingolimod treatment. It is designed to evaluate the safety and tolerability of this combination in this patient population based on an immunomodulatory treatment with fingolimod.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see Appendix 4)

• Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix 8)

• Patients with high disease activity despite treatment with a disease modifying therapy (> 1 relapse in the previous year, > 9 hyperintense T2 lesions or > 1 Gd-enhancing lesion or "non-responding" which could be defined as unchanged or increased relapse rate or ongoing severe relapses compared to previous year)or patients with rapidly evolving severe RRMS (e.g. > 2 relapses with disease progression in one year and > 1 Gd-enhancing lesion or with a significant increase in T2 lesions compared to a recent MRI)

• Depression according to ICD-10 criteria

• Mild-moderate depression assessed by BDI-II score between 14-28 inclusively measured before study inclusion and before fingolimod is administered

Exclusion Criteria:

• Patients with a history of chronic disease of the immune system other than MS which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome. Patients with Crohns disease or ulcerative colitis are excluded without exception

• History or presence of malignancy (other than localized basal or squamous cell carcinoma of the skin)

• Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests

• Negative for varicella-zoster virus IgG antibodies at Screening

• Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-ß, glatiramer acetate); however no washout is needed for DMDs prior to start of fingolimod

• Patients who are or have been treated with:

• immunoglobulins and/or monoclonal antibodies (including natalizumab) within 3 months prior to start of fingolimod

• Systemically applied corticosteroids or adrenocorticotropic hormones (ACTH) within 1 month prior to start of fingolimod (nevertheless, topical application is permitted);

• Immunosuppressive medications such as azathioprine or methotrexate, within 3 months prior to start of fingolimod;

• Cyclophosphamid and mitoxantrone within 6 months prior to start of fingolimod

• cladribine at any time

• current psychological or pharmacological treatment for depression (MAO inhibitors in particular), a washout period of 1 month prior start of fingolimod is required

• current treatment with linezolid, a washout period of 1 month prior start of fingolimod is required

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Venlafaxine
Venlafaxine starting dose was 75 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 150 Mg
• Fluoxetine
Fluoxetine starting dose was 20 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 40 Mg
• Citalopram
Citalopram starting dose was 20 mg and given once daily for at least 7 days and a maximum of 28 days. Dosage was increased afterwards to the individual final dose given once daily, i.e. after at least 7 days and a maximum of 28 days, patients were titrated to their maximum dose of 40 Mg
• Fingolimod
Dosage of 0.5 mg per capsule (hard gelatin capsules) was taken p.o. once daily. Fingolimod was supplied in bottles containing 35 capsules each.

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Achim
Germany	Novartis Investigative Site	Altenholz-Stift
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Bad Honnef
Germany	Novartis Investigative Site	Baesweiler
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bremerhaven
Germany	Novartis Investigative Site	Butzbach
Germany	Novartis Investigative Site	Grevenbroich
Germany	Novartis Investigative Site	Heidenheim
Germany	Novartis Investigative Site	Klingenmünster
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Merzig
Germany	Novartis Investigative Site	Nienburg
Germany	Novartis Investigative Site	Oberhausen
Germany	Novartis Investigative Site	Oldenburg
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Schwalmstadt-Treysa
Germany	Novartis Investigative Site	Stadtroda
Germany	Novartis Investigative Site	Tübingen
Germany	Novartis Investigative Site	Weil am Rhein
Germany	Novartis Investigative Site	Zwickau

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death	In this analysis patients with all (serious and non-serious) adverse events, and death were reported.; See Safety Section.	21 weeks	Yes