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

This study has been terminated.
(Due to slow enrollment the study was terminated early)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01436643
First received: September 16, 2011
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Depression
Relapsing-remitting Multiple Sclerosis
Drug: Venlafaxine
Drug: Fluoxetine
Drug: Citalopram
Drug: Fingolimod
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants Who Experienced Adverse Events, Serious Adverse Events and Death [ Time Frame: 21 weeks ] [ Designated as safety issue: Yes ]

    In this analysis patients with all (serious and non-serious) adverse events, and death were reported.

    See Safety Section.



Enrollment: 54
Study Start Date: November 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
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
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.
Experimental: 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
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
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.
Experimental: 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
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
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01436643

Locations
Germany
Novartis Investigative Site
Achim, Germany, 28832
Novartis Investigative Site
Altenholz-Stift, Germany, 24161
Novartis Investigative Site
Aschaffenburg, Germany, 63739
Novartis Investigative Site
Bad Honnef, Germany, 53604
Novartis Investigative Site
Baesweiler, Germany, 52499
Novartis Investigative Site
Berlin, Germany, 12621
Novartis Investigative Site
Bielefeld, Germany, 33602
Novartis Investigative Site
Bielefeld, Germany, 33647
Novartis Investigative Site
Bochum, Germany, 44787
Novartis Investigative Site
Bremerhaven, Germany, 27574
Novartis Investigative Site
Butzbach, Germany, 35510
Novartis Investigative Site
Grevenbroich, Germany, 41515
Novartis Investigative Site
Heidenheim, Germany, 89518
Novartis Investigative Site
Klingenmünster, Germany, 76889
Novartis Investigative Site
Leipzig, Germany, 04275
Novartis Investigative Site
Merzig, Germany, 66663
Novartis Investigative Site
Nienburg, Germany, 31582
Novartis Investigative Site
Oberhausen, Germany, 46045
Novartis Investigative Site
Oldenburg, Germany, 26122
Novartis Investigative Site
Potsdam, Germany, 14471
Novartis Investigative Site
Schwalmstadt-Treysa, Germany, 34613
Novartis Investigative Site
Stadtroda, Germany, 07646
Novartis Investigative Site
Tübingen, Germany, 72076
Novartis Investigative Site
Weil am Rhein, Germany, 79576
Novartis Investigative Site
Zwickau, Germany, 08060
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01436643     History of Changes
Other Study ID Numbers: CFTY720DDE06, 2011-001692-39
Study First Received: September 16, 2011
Results First Received: September 1, 2014
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:
Depression
Multiple Sclerosis
Fingolimod
Venlafaxine
Fluoxetine

Additional relevant MeSH terms:
Depression
Depressive Disorder
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Behavioral Symptoms
Mood Disorders
Mental Disorders
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Venlafaxine
Citalopram
Fluoxetine
Dexetimide
Fingolimod
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs

ClinicalTrials.gov processed this record on October 01, 2014