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

NCT ID: NCT01436643

Last Updated: 2014-09-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-09-30

Brief 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.

Conditions

Depression; Relapsing-remitting Multiple Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fluoxetine and Fingolimod

Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Fluoxetine, supplied in blistered packs containing 20 tablets; starting dose 20 mg; final dose 40 mg

Group Type: EXPERIMENTAL

Fluoxetine

Intervention Type: DRUG

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

Fingolimod

Intervention Type: DRUG

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.

Venlafaxine and Fingolimod

Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Venlafaxine, supplied in blistered packs containing 14 capsules; starting dose 75 mg; final dose 150 mg

Group Type: EXPERIMENTAL

Venlafaxine

Intervention Type: DRUG

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

Fingolimod

Intervention Type: DRUG

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.

Citalopram and Fingolimod

Fingolimod 0.5 mg per capsule(hard gelatin capsules) was taken p.o. once daily. Citalopram, supplied in blistered packs containing 20 tablets; starting dose 20 mg, final dose 40 mg

Group Type: EXPERIMENTAL

Citalopram

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

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-β, 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Altenholz-Stift, Germany, Germany

Novartis Investigative Site

Achim, , 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, , Germany

Countries

Germany

Other Identifiers

2011-001692-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CFTY720DDE06

Identifier Type: -

Identifier Source: org_study_id