Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01466114
• Date of registration: 31/10/2011
• Prospective Registration: No
• Primary sponsor: University of California, Los Angeles
• Public title: Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition
• Scientific title: A Double-Blind, Placebo Controlled Trial of Estriol Treatment in Women With Multiple Sclerosis: Effect on Cognition.
• Date of first enrolment: October 2011
• Target sample size: 64
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT01466114
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Mike Montag, M.S.

• Name: Mike Montag, M.S.

• Name: Rhonda Voskuhl, M.D.
• Affiliation: University of California, Los Angeles

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of clinically definite or MacDonald criteria relapsing-remitting multiple
sclerosis, secondary-progressive multiple sclerosis or primary-progressive multiple
sclerosis.

- No relapse within 30 days before day of trial enrollment (month 0 visit). If steroids
given for relapse, then the month 0 visit must be 30 days after last steroid dose.

- Females age 18 to 55, inclusive.

- Expanded Disability Status Score (EDSS) = 0.0 to 6.0.

- Screening PASAT (3-second) score 25-50, inclusive.

- Must be mentally competent enough to comply with study guidelines and give informed
consent.

- Must be willing and able to travel to the study center at frequencies in the protocol
for a total period of 12 months.

- Patients must be on no treatment or be on a stable dose of one of the following agents
for a minimum of 3 months duration prior to the month 0 visit: Copaxone®, Betaseron®
(or Extavia®), Rebif®, Avonex®, PLEGRITY®, Ocrelizumab, Rituximab, Gilenya®, Aubagio®,
or Tecfidera®. The time spent in the screening period may serve as part of this
3-month period.

- Patients who are currently being treated with ACTH, corticosteroids, intravenous
immunoglobulins (IVIG), plasma exchange, Lipitor® or minocycline may be included.

- If patients plan to start treatment with Copaxone® or an interferon [Betaseron® (or
Extavia®), Rebif®, Avonex®, PLEGRITY®], Ocrelizumab, Rituximabor an oral agent
[Gilenya®, Aubagio® or Tecfidera®] and then they must be on for at least 3 months
prior to month 0 (as above).

Exclusion Criteria:

- Males

- Subjects on oral contraceptives (OCP), hormone replacement therapy (HRT) other sex
hormones during screening and during the 12-month study period (Mirena® IUD is
permitted).

- Females who are pregnant or who plan to become pregnant during the 12 months of
enrollment, who wish to become pregnant within 3 months following completion of the
study, or who will be within 6 months post partum at the day of first enrollment visit
(month 0).

- Females who plan to breastfeed after first enrollment visit (month 0).

- Fertile sexually active women who are unwilling to practice reliable barrier methods
of contraception other than oral contraceptives (i.e. condom, diaphragm, IUDs Note:
Hormonal IUD [Mirena®] is permitted).

- Patients with surgical ovariectomy with no hormone replacement for 1 year or more.

- Menopause with no hormone replacement for 3 years or more prior to the first
enrollment visit.

- Patients who smoke at any time during screening or during the 12 month study period.

- Patients who have serious pulmonary, renal, gastrointestinal, hepatic, immunologic,
infectious, neoplastic, major psychiatric disease (major depression, schizophrenia),
endocrine disease (including major diabetes, thyroid disease), or gynecologic disease,
including but not limited to those with: Thrombophlebitis or thromboembolic disorders,
a past history of deep vein thrombophlebitis or thromboembolic disorders, cerebral
vascular or coronary artery disease, migraine with focal aura, known or suspected
carcinoma of the breast, carcinoma of the endometrium or other known or suspected
estrogen-dependent neoplasia, undiagnosed abnormal genital bleeding, polycystic ovary
disease, amenorrhea of unknown etiology, cholestatic jaundice of pregnancy or jaundice
with prior birth control pill use, acute or chronic hepatocellular disease with
abnormal liver function, hepatic adenomas or carcinomas, known or suspected pregnancy,
known hypersensitivity to birth control pill Copaxone or Betaseron use.

- B12 level < 200.

- Drug abuse within the past five years.

- Conditions that would interfere with assessing neurologic functions such as deforming
arthritis or a major amputation.

- Have at any time been treated with total lymphoid irradiation, monoclonal antibody, T
cell vaccination, cladribine, bone marrow transplantation, azathioprine,
cyclophosphamide, methotrexate, mitoxantrone, or cyclosporine.

- Have been treated with natalizumab (Tysabri®) in the 6 months prior to screening.

- Positive titers to HIV in the past.

- Previous serious adverse effects with estrogen treatment.

- Patients who participated in the previous multi-center estriol trial for RRMS ("A
Combination Trial of Copaxone plus Estriol in RRMS").



Age minimum: 18 Years
Age maximum: 55 Years
Gender: Female

Health Condition(s) or Problem(s) studied

Secondary-progressive Multiple Sclerosis

Primary-progressive Multiple Sclerosis

Relapsing-remitting Multiple Sclerosis

Intervention(s)

Drug: estriol

Drug: Norethindrone

Other: Placebo

Other: Progestin Placebo

Primary Outcome(s)

Change from baseline in cognitive function assessed by Paced Serial Addition Test (PASAT). [Time Frame: 1 year]

Secondary Outcome(s)

Change from baseline in cognitive function as assessed by cognitive evoked potentials, measured in milliseconds. [Time Frame: 1 year]

Determine safety by assessing the number of subjects with adverse events with combination treatment as compared to placebo. [Time Frame: 1 year]

Change from baseline in cognitive function as assessed by a brief battery of cognitive tests. [Time Frame: 1 year]

Change from baseline in standard MS outcome measures. [Time Frame: 1 year]

Secondary ID(s)

11-002055

Source(s) of Monetary Support

Please refer to primary and secondary sponsors