Fluoxetine in progressive multiple sclerosis: a placebo-controlled randomised trial

ISRCTN	ISRCTN38456328
DOI	https://doi.org/10.1186/ISRCTN38456328
Protocol serial number	NL583, NTR639
Sponsor	University Medical Center Groningen (UMCG) (The Netherlands)
Funder	Innovatiefonds University Medical Center Groningen (The Netherlands)

Submission date: 15/09/2006
Registration date: 15/09/2006
Last edited: 07/01/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr J.P. Mostert
Scientific

University Medical Center Groningen (UMCG)
P.O. Box 30001
Groningen
9700 RB
Netherlands

Phone	+31 (0)50 3614817 / +31 (0)50 3612430
Email	j.p.mostert@neuro.umcg.nl

Study information

Primary study design	Interventional
Study design	Placebo controlled, randomised trial
Secondary study design	Randomised controlled trial
Scientific title	Fluoxetine in progressive multiple sclerosis: a placebo-controlled randomised trial
Study objectives	Fluoxetine has in animals and cell cultures neuroprotective properties. We test whether fluoxetine is able to reduce progression in patients with Multiple Sclerosis (MS).
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Multiple Sclerosis (MS)
Intervention	1. Treatment with fluoxetine 40 mg/day or placebo during 2 years 2. Every 3 months clinical evaluation (EDSS, Multiple Sclerosis Functional Composite [MSFC], Ambulatory Index [AI]) 3. Yearly cerebral MRI 4. Yearly questionnaires (Guys Neurological Disability Scale, BDI, Short Form [SF-36] health survey)
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Fluoxetine
Primary outcome measure(s)	Number of patients with progression in two years. Progression is defined as: 1. Persistent (two or more follow-up assessments) worsening of EDSS with 1.0 point with basis EDSS 3.0 to 5.0 or persistent (two or more follow-up assessments) worsening of EDSS with 0.5 with basis EDSS 5.5 to 6.5 2. Or persistent (two or more follow-up assessments) worsening of 9-Hole Peg Test (9-HPT) with 20% compared to baseline measurement 3. Or persistent (two or more follow-up assessments) worsening of the AI of one point with a basis AI between two and six
Key secondary outcome measure(s)	1. Change in the following MRI measurements: a. T2 lesion volume b. T1 lesion volume (black holes) c. Brain atrophy d. N-Acetyl Aspartate (NAA) e. Apparent Diffusion Co-efficient (ADC) and Fractional Anisotropy (FA) histogram values 2. Change in EDSS, MSFC, SF-36, Guys Neurological Disability Scale, BDI, Family Intrusiveness Scale (FIS) 3. Time (in months) to progression
Completion date	01/05/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	60
Total final enrolment	42
Key inclusion criteria	1. Written informed consent 2. Age 18 to 65 3. MS according to the McDonald criteria or primary progressive MS according to the Thompson criteria 4. Expanded Disability Status Scale (EDSS) 3.0 to 6.5 inclusive 5. Documented progression in the last two years unrelated to clinical exacerbations in the last two years
Key exclusion criteria	1. Contra-indication Magnetic Resonance Imaging (MRI) (e.g., metal, claustrophobia) 2. Women of childbearing potential, who are not using a medically accepted safe method of contraception 3. Pregnancy or women who are lactating 4. Moderate to severe depression measured as a score of more than 18 on the Beck Depression Inventory (BDI) 5. Treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) 6. Treatment with Monoamine Oxidase (MAO)-inhibitors, oral anticoagulants, Serotonin (5-HT) agonists and/or lithium 7. Treatment with interferon ß, glatiramer acetate, plasmapheresis, natalizumab, other immunomodulatory drugs, or immunosuppressive drugs including azathioprine, cyclophosphamide and methotrexate, within six months of week zero 8. Treatment with corticosteroids within three months of week zero 9. Renal failure 10. Neurological disorder other than MS, acute or chronic infection, malignant neoplasm or metastasis, cardiovascular disorder or pulmonary disorder, severe intercurrent systemic disease, or any other disease that interferes with the assessments
Date of first enrolment	01/05/2006
Date of final enrolment	01/05/2009

Locations

Countries of recruitment

Netherlands

Study participating centre

University Medical Center Groningen (UMCG)

Groningen
9700 RB
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	29/07/2013	06/01/2021	Yes	No

Editorial Notes

07/01/2021: The NTR numbers have been added.
06/01/2021: Publication reference and total final enrolment added.