Clinical trial NCT01436643: Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Depression
Relapsing-remitting Multiple Sclerosis
Keywords: Depression
Multiple Sclerosis
Fingolimod
Venlafaxine
Fluoxetine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-09-20
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death
timeFrame: 21 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Achim
country: Germany
facility: Novartis Investigative Site
city: Altenholz-Stift
country: Germany
facility: Novartis Investigative Site
city: Aschaffenburg
country: Germany
facility: Novartis Investigative Site
city: Bad Honnef
country: Germany
facility: Novartis Investigative Site
city: Baesweiler
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bremerhaven
country: Germany
facility: Novartis Investigative Site
city: Butzbach
country: Germany
facility: Novartis Investigative Site
city: Grevenbroich
country: Germany
facility: Novartis Investigative Site
city: Heidenheim
country: Germany
facility: Novartis Investigative Site
city: Klingenmünster
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Merzig
country: Germany
facility: Novartis Investigative Site
city: Nienburg
country: Germany
facility: Novartis Investigative Site
city: Oberhausen
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Schwalmstadt-Treysa
country: Germany
facility: Novartis Investigative Site
city: Stadtroda
country: Germany
facility: Novartis Investigative Site
city: Tübingen
country: Germany
facility: Novartis Investigative Site
city: Weil am Rhein
country: Germany
facility: Novartis Investigative Site
city: Zwickau
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: