Clinical trial NCT00151801: Safety and Tolerability of Interferon-Beta-1a and Estroprogestins Association in MS Patients
Official title: Safety and Tolerability of Oral Two-Doses Estroprogestins Associated With Interferon-Beta 1a in Patients With Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: multiple sclerosis
estroprogestins
interferon-beta
sex hormones
MRI
Lead sponsor: S. Andrea Hospital
Sponsor class: OTHER
First posted: 2005-09-09
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clinical and experimental evidences suggests an immunomodulatory effect of sex hormones in multiple sclerosis.

The role of oral estroprogestins in the pathogenesis and in the clinical course of the disease is actually unknown.

The aim of the study is to investigate safety and tolerability of association of estroprogestins in two different doses with interferon-beta 1a in patients with relapsing-remitting multiple sclerosis.

Detailed description: Phase 2, randomised, single blind, three arms study.

Follow-up of 24 months.

The study will include relapsing-remitting multiple sclerosis female patients.

Patients will be equally randomised into three groups: 1) patients treated with IFN-beta 1a (44 mcg for three times a week), 2) patients treated with IFN-beta 1a and lower-dose estroprogestins (desogestrel 150 mcg, etinilestradiol 20 mcg), 3) patients treated with IFN-beta 1a and higher-dose estroprogestins (desogestrel 25 mcg, etinilestradiol 40 mcg).

Safety and tolerability of the treatment will be evaluated using neurological examination and MRI analysis.

A complete neurological examination (with EDSS) will be performed at month 0, 6, 12, 18 and 24.

MRI examination will be assessed at baseline and at month 12 and 24. In the same day of MRI examination we'll collect blood samples for hormonal analysis (we'll measure sex hormones in the follicular and in the luteal phase of a single menstrual cycle).

During the follow-up patients will be evaluated also with: MS-Functional Composite at month 0, 6, 12, 18, 24; neuropsychological evaluation at month 0, 12, 24; Fatigue Severity Scale at month 0, 12, 24; Hamilton Depression Scale at month 0, 12, 24; Quality of Life scale (MSQOL54) at month 0, 12, 24.

Eligibility criteria: Inclusion Criteria:

* Female patients
* Clinically definite relapsing-remitting MS according to the McDonald criteria
* Age between 18-40 y.o.
* EDSS from 0 to 4.0, inclusive

Exclusion Criteria:

* History of migraine or thromboembolic events
* Reproductive system disorders
* Pregnancy or suspension of pregnancy within 12 months prior to randomisation
* Prior use of estroprogestins within the last 3 months prior to randomisation
* Prior use of immunosuppressive drugs within the last 12 months prior to randomisation
* Prior use of immunomodulating drugs within the last 6 months prior to randomisation
* Prior use of corticosteroids within the last 3 months prior to randomisation
* Have clinical relapse 30 days prior to randomisation

Primary outcomes:
measure: Safety assessment at 6, 12, 18 and 24 months, including adverse events, physical examination and laboratory parameters
measure: Relapse rate at 6, 12, 18 and 24 months,
measure: EDSS progression at 12 and 24 months,
measure: MS functional composite score at 12 and 24 months,
Secondary outcomes:
measure: Number and volume of new gad-enhancing lesions at 12 and 24 months
measure: Number of new T1 and T2 lesions at 12 and 24 months
measure: Brain volume changes at 12 and 24 months
measure: Neuropsychological examination at 0, 12, 24 months
measure: Hamilton scale for depression score at 0, 12, 24 months
measure: MS Quality of Life scale score(MSQOL54)at 0, 12, 24 months
measure: Fatigue Severity Scale score at 0, 12, 24 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Department of Neurology - University of Rome La Sapienza
Study officials:
affiliation: Department of Neurological Science University of Rome "La Sapienza"
name: Valentina Tomassini, MD
role: STUDY_CHAIR
affiliation: Department of Neurological Science, University of Rome "La Sapienza"
name: Fabiana Marinelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neurological Science, University of Rome "La Sapienza"
name: Carlo Pozzilli, MD
role: STUDY_DIRECTOR
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citation: Pozzilli C, Tomassini V, Marinelli F, Paolillo A, Gasperini C, Bastianello S. 'Gender gap' in multiple sclerosis: magnetic resonance imaging evidence. Eur J Neurol. 2003 Jan;10(1):95-7. doi: 10.1046/j.1468-1331.2003.00519.x.
citation: De Giglio L, Marinelli F, Barletta VT, Pagano VA, De Angelis F, Fanelli F, Petsas N, Pantano P, Tomassini V, Pozzilli C. Effect on Cognition of Estroprogestins Combined with Interferon Beta in Multiple Sclerosis: Analysis of Secondary Outcomes from a Randomised Controlled Trial. CNS Drugs. 2017 Feb;31(2):161-168. doi: 10.1007/s40263-016-0401-0.