Safety and Tolerability of Interferon-Beta-1a and Estroprogestins Association in MS Patients

Multiple Sclerosis Clinical Trial

Official title:

Safety and Tolerability of Oral Two-Doses Estroprogestins Associated With Interferon-Beta 1a in Patients With Relapsing-Remitting Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00151801
• Other study ID #: NEU - PIL - 03
• Status: Recruiting
• Phase: Phase 2
• First received: September 8, 2005
• Last updated: September 8, 2005
• Start date: May 2002
• Est. completion date: December 2008

Study information

• Verified date: September 2005
• Source: S. Andrea Hospital
• Contact: Carlo Pozzilli, MD
• Phone: +39-06-49914716
• Email: carlo.pozzilli[@]uniroma1.it
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• estroprogestins

• interferon-beta 1a

Locations

Country	Name	City	State
Italy	Department of Neurology - University of Rome La Sapienza	Rome

Sponsors (1)

Lead Sponsor	Collaborator
S. Andrea Hospital

Country where clinical trial is conducted

Italy, 

References & Publications (8)

Bansil S, Lee HJ, Jindal S, Holtz CR, Cook SD. Correlation between sex hormones and magnetic resonance imaging lesions in multiple sclerosis. Acta Neurol Scand. 1999 Feb;99(2):91-4. — View Citation

De Cicco Nardone F, Rossiello F, Iacopino F, Benedetto MT, Cinque B, Dell'Acqua S, Sica G. Effects of interferon-beta on steroid receptors, prostaglandins and enzymatic activities in human endometrial cancer. Anticancer Res. 1996 Jan-Feb;16(1):161-9. — View Citation

Hawkins SA, McDonnell GV. Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychiatry. 1999 Aug;67(2):148-52. — View Citation

Hernán MA, Hohol MJ, Olek MJ, Spiegelman D, Ascherio A. Oral contraceptives and the incidence of multiple sclerosis. Neurology. 2000 Sep 26;55(6):848-54. — View Citation

Kim S, Liva SM, Dalal MA, Verity MA, Voskuhl RR. Estriol ameliorates autoimmune demyelinating disease: implications for multiple sclerosis. Neurology. 1999 Apr 12;52(6):1230-8. — View 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. — View Citation

Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998 Nov 7;352(9139):1498-504. Erratum in: Lancet 1999 Feb 20;353(9153):678. — View Citation

Zorgdrager A, De Keyser J. Menstrually related worsening of symptoms in multiple sclerosis. J Neurol Sci. 1997 Jul;149(1):95-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety assessment at 6, 12, 18 and 24 months, including adverse events, physical examination and laboratory parameters
Primary	Relapse rate at 6, 12, 18 and 24 months,
Primary	EDSS progression at 12 and 24 months,
Primary	MS functional composite score at 12 and 24 months,
Secondary	Number and volume of new gad-enhancing lesions at 12 and 24 months
Secondary	Number of new T1 and T2 lesions at 12 and 24 months
Secondary	Brain volume changes at 12 and 24 months
Secondary	Neuropsychological examination at 0, 12, 24 months
Secondary	Hamilton scale for depression score at 0, 12, 24 months
Secondary	MS Quality of Life scale score(MSQOL54)at 0, 12, 24 months
Secondary	Fatigue Severity Scale score at 0, 12, 24 months