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Safety and Tolerability of Interferon-Beta-1a and Estroprogestins Association in MS Patients
This study is currently recruiting participants.
Verified by S. Andrea Hospital, September 2005
First Received: September 8, 2005   No Changes Posted
Sponsored by: S. Andrea Hospital
Information provided by: S. Andrea Hospital
ClinicalTrials.gov Identifier: NCT00151801
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: estroprogestins
Drug: interferon-beta 1a
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Single Blind, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title: Safety and Tolerability of Oral Two-Doses Estroprogestins Associated With Interferon-Beta 1a in Patients With Relapsing-Remitting Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by S. Andrea Hospital:

Primary Outcome Measures:
  • Safety assessment at 6, 12, 18 and 24 months, including adverse events, physical examination and laboratory parameters
  • Relapse rate at 6, 12, 18 and 24 months,
  • EDSS progression at 12 and 24 months,
  • MS functional composite score at 12 and 24 months,

Secondary Outcome Measures:
  • Number and volume of new gad-enhancing lesions at 12 and 24 months
  • Number of new T1 and T2 lesions at 12 and 24 months
  • Brain volume changes at 12 and 24 months
  • Neuropsychological examination at 0, 12, 24 months
  • Hamilton scale for depression score at 0, 12, 24 months
  • MS Quality of Life scale score(MSQOL54)at 0, 12, 24 months
  • Fatigue Severity Scale score at 0, 12, 24 months

Estimated Enrollment: 200
Study Start Date: May 2002
Estimated Study Completion Date: December 2008
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

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00151801

Contacts
Contact: Carlo Pozzilli, MD +39-06-49914716 carlo.pozzilli@uniroma1.it
Contact: Fabiana Marinelli, MD +39-338-2955443 fabiana.marinelli@uniroma1.it

Locations
Italy
Department of Neurology - University of Rome La Sapienza Recruiting
Rome, Italy, 00100
Contact: Carlo Pozzilli, MD     +39-06-49914716     carlo.pozzilli@uniroma1.it    
Contact: Fabiana Marinelli, MD     +39-338-2955443     fabiana.marinelli@uniroma1.it    
Principal Investigator: Fabiana Marinelli, MD            
Sub-Investigator: Laura De Giglio, MD            
Sponsors and Collaborators
S. Andrea Hospital
Investigators
Study Chair: Valentina Tomassini, MD Department of Neurological Science University of Rome "La Sapienza"
Principal Investigator: Fabiana Marinelli, MD Department of Neurological Science, University of Rome "La Sapienza"
Study Director: Carlo Pozzilli, MD Department of Neurological Science, University of Rome "La Sapienza"
  More Information

Publications:
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.
Zorgdrager A, De Keyser J. Menstrually related worsening of symptoms in multiple sclerosis. J Neurol Sci. 1997 Jul;149(1):95-7.
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.
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.
Hernan 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.
[No authors listed] 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.
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.
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.

Study ID Numbers: NEU - PIL - 03
Study First Received: September 8, 2005
Last Updated: September 8, 2005
ClinicalTrials.gov Identifier: NCT00151801     History of Changes
Health Authority: Italy: Ministry of Health

Keywords provided by S. Andrea Hospital:
multiple sclerosis
estroprogestins
interferon-beta
sex hormones
MRI

Study placed in the following topic categories:
Anti-Infective Agents
Interferon Type I, Recombinant
Immunologic Factors
Hormone Antagonists
Estradiol valerate
Hormones, Hormone Substitutes, and Hormone Antagonists
Estradiol 17 beta-cypionate
Hormones
Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis
Estradiol 3-benzoate
Interferon beta 1a
Polyestradiol phosphate
Autoimmune Diseases of the Nervous System
Estrogens
Autoimmune Diseases
Demyelinating Diseases
Interferons
Interferon-beta
Adjuvants, Immunologic
Ethinyl Estradiol
Sclerosis
Antiviral Agents
Angiogenesis Inhibitors
Estradiol
Demyelinating Autoimmune Diseases, CNS

Additional relevant MeSH terms:
Anti-Infective Agents
Interferon Type I, Recombinant
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Multiple Sclerosis
Therapeutic Uses
Interferon beta 1a
Growth Inhibitors
Angiogenesis Modulating Agents
Autoimmune Diseases of the Nervous System
Estrogens
Autoimmune Diseases
Immune System Diseases
Demyelinating Diseases
Growth Substances
Interferons
Nervous System Diseases
Adjuvants, Immunologic
Interferon-beta
Ethinyl Estradiol
Sclerosis
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Demyelinating Autoimmune Diseases, CNS

ClinicalTrials.gov processed this record on August 30, 2009