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

Novartis

Status and phase: Terminated; Phase 4

Conditions: Depression; Relapsing-remitting Multiple Sclerosis

Treatments: Drug: Citalopram; Drug: Fingolimod; Drug: Venlafaxine; Drug: Fluoxetine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01436643

2011-001692-39 (EudraCT Number)

CFTY720DDE06

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Other protocol-defined inclusion/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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54 participants in 3 patient groups

Fluoxetine and Fingolimod

Experimental group

Description:

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

Treatment:

Drug: Fingolimod

Drug: Fluoxetine

Venlafaxine and Fingolimod

Experimental group

Description:

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

Treatment:

Drug: Fingolimod

Drug: Venlafaxine

Citalopram and Fingolimod

Experimental group

Description:

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

Treatment:

Drug: Citalopram

Drug: Fingolimod