Trial record 2 of 2 for:    estriol ms

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

This study is currently recruiting participants.
Verified July 2013 by University of California, Los Angeles
Sponsor:
Collaborator:
Synthetic Biologics (formerly Adeona Pharmaceuticals)
Information provided by (Responsible Party):
Rhonda Voskuhl, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01466114
First received: October 31, 2011
Last updated: July 17, 2013
Last verified: July 2013

October 31, 2011
July 17, 2013
October 2011
December 2015   (final data collection date for primary outcome measure)
Change from baseline in cognitive function assessed by Paced Serial Addition Test (PASAT). [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Processing speed will be assessed by PASAT. Numerical test scores (ranging from 0-60) will be acquired, then percent change for each subject at trial conclusion as compared to baseline will be determined. Whether greater improvement as expressed as percent change occurs in the estriol group as compared to the placebo group will be determined.
cognitive function assessed by Paced Serial Addition Test (PASAT) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Processing speed will be assessed by PASAT. Numerical test scores (ranging from 0-60) will be acquired, then percent change for each subject at trial conclusion as compared to baseline will be determined. Whether greater improvement as expressed as percent change occurs in the estriol group as compared to the placebo group will be determined.
Complete list of historical versions of study NCT01466114 on ClinicalTrials.gov Archive Site
  • Change from baseline in cognitive function as assessed by cognitive evoked potentials, measured in milliseconds. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Cognitive evoked potentials will be recorded in msecs for each subject at baseline and conclusion. The percent improvement as conclusion as compared to baseline for each subject will be determined. Group comparisons will reveal whether the percent improvement is greater in the estriol treated group as compared to the placebo treated group.
  • Change from baseline in standard MS outcome measures. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Determine whether the combination treatment has an effect on standard MS outcome measures (relapses, EDSS, 25 foot walk test, 9 hole peg test, low contrast visual acuity, MS Quality of Life, Modified Fatigue Impact Scare, Beck Depression Inventory.
  • Determine safety by assessing the number of subjects with adverse events with combination treatment as compared to placebo. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Determine whether the combination treatment is safe (based on neurologic exams, laboratory tests (Chemistries, CBC), and gynecologic exams (breast and gynecologic exams).
  • Change from baseline in cognitive function as assessed by a brief battery of cognitive tests. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A brief battery of cognitive tests will be administered including: Processing speed: SDMT; Visual memory: 7/24 Spatial Recall Test, Benton Forms F & G; Verbal memory: Buschke Selective Reminding Test, Verbal Paired Associates; Language: Word List Generation. Each subject will be tested at baseline, month 6 and conclusion. Percent change at conclusion as compared to baseline will be determined in each subject. Group comparisons will reveal which cognitive test within the battery had greater improvement in the estriol treated group as compared to the placebo treated group.
  • cognitive function as assessed by cognitive evoked potentials [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Cognitive evoked potentials will be recorded in msecs for each subject at baseline and conclusion. The percent improvement as conclusion as compared to baseline for each subject will be determined. Group comparisons will reveal whether the percent improvement is greater in the estriol treated group as compared to the placebo treated group.
  • effect on standard MS outcome measures [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Determine whether the combination treatment has an effect on standard MS outcome measures (relapses, EDSS, 25 foot walk test, 9 hole peg test, low contrast visual acuity, MS Quality of Life, Modified Fatigue Impact Scare, Beck Depression Inventory.
  • safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Determine whether the combination treatment is safe (based on neurologic exams, laboratory tests (Chemistries, CBC), and gynecologic exams (breast and gynecologic exams).
  • Brain MRI [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Whole brain atrophy, T2 lesion volume, gadolinium enhancing lesion number and volume will be assessed on brain MRI at baseline and conclusion in each subject. Comparisons for each outcome for each subject at these two timepoints will be made. Group comparisons will reveal whether there is less brain atrophy, less T2 volume, and less gadolinium enhancing lesion number and volume in the estriol treated group as compared to the placebo group.
  • cognitive function assessed by a brief battery of cognitive tests [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A brief battery of cognitive tests will be administered including: Processing speed: SDMT; Visual memory: 7/24 Spatial Recall Test, Benton Forms F & G; Verbal memory: Buschke Selective Reminding Test, Verbal Paired Associates; Language: Word List Generation. Each subject will be tested at baseline, month 6 and conclusion. Percent change at conclusion as compared to baseline will be determined in each subject. Group comparisons will reveal which cognitive test within the battery had greater improvement in the estriol treated group as compared to the placebo treated group.
Not Provided
Not Provided
 
Estriol Treatment in Multiple Sclerosis (MS): Effect on Cognition
A Double-Blind, Placebo Controlled Trial of Estriol Treatment in Women With Multiple Sclerosis: Effect on Cognition.

Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments targeting cognitive function in Multiple Sclerosis. This trial will ascertain whether treatment with an estrogen pill, used in combination with standard MS anti-inflammatory drugs, can improve cognitive testing as compared to treatment with a placebo pill in combination with standard anti-inflammatory drugs in women with MS.

Approximately 50% of people diagnosed with Multiple Sclerosis (MS) will develop problems with cognition. Currently, there are no FDA-approved treatments for cognitive function in Multiple Sclerosis. Multiple sclerosis relapses are known to be significantly decreased by approximately 80% during late pregnancy. This disease improvement may be due to estriol, an estrogen unique to pregnancy. Estriol blood levels go from undetectable levels prior to pregnancy, increase during pregnancy and reach highest levels during late pregnancy. Further, estrogen treatment has been shown to have favorable effects on cognition in animal models of other neurological diseases. This proposal will establish whether oral treatment with estriol, induces an improvement in cognitive functioning in subjects with multiple sclerosis when used in combination with the major FDA-approved standard treatments for MS, (Betaseron® (or Extavia®), Rebif®, Avonex®, Copaxone®, Gilenya®, Aubagio®, or Tecfidera®).

The combination of standard MS treatment plus estriol pill (8 mg per day) will be compared to standard MS treatment plus placebo in a double-blinded fashion. The duration of treatment will be one year and the primary outcome measure will be cognitive testing processing speed ability.

Secondary outcomes will be improvement in other cognitive tests, brain MRIs, cognitive evoked potentials, as well as relapse rates and disability measures (EDSS, 25 foot walk, 9 hole peg test, low contrast visual acuity, MS Quality of Life, Modified Fatigue Impact Scale, Beck Depression Inventory, Level of Activity using accelerometry). Safety measures (blood tests and gynecologic evaluations) will also be followed. The overall goal of this study will be the development of an oral treatment, estriol, to improve cognitive function in MS.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Relapsing-remitting Multiple Sclerosis
  • Secondary-progressive Multiple Sclerosis
  • Primary-progressive Multiple Sclerosis
  • Drug: estriol
    4 capsules of 2 mg (total of 8 mg) PO QD
    Other Name: Synapause
  • Other: Placebo
    4 capsules PO QD
  • Drug: Norethindrone
    Starting at month 6, and at Months 9 and 12: subjects who are on estriol (Group A) take 0.7 mg PO QD for 2 weeks.
    Other Name: Progestin
  • Other: Progestin Placebo
    Starting at Month 6 and at Months 9 and 12: subjects who are on placebo (Group B) take a second progestin placebo pill PO QD for 2 weeks.
  • Experimental: Group A: Estriol
    Standard MS Treatment + Estriol
    Interventions:
    • Drug: estriol
    • Drug: Norethindrone
  • Placebo Comparator: Group B: Placebo
    Standard MS Treatment + Placebo
    Interventions:
    • Other: Placebo
    • Other: Progestin Placebo
Ziehn MO, Avedisian AA, Dervin SM, O'Dell TJ, Voskuhl RR. Estriol preserves synaptic transmission in the hippocampus during autoimmune demyelinating disease. Lab Invest. 2012 Aug;92(8):1234-45. doi: 10.1038/labinvest.2012.76. Epub 2012 Apr 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
64
April 2016
December 2015   (final data collection date for primary outcome measure)

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 50, 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 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®, or Avonex®, Gilenya®, Aubagio®, or BG-12. 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.
  • Patients who are not currently treated with one of the above treatments may only be included if they plan to start Copaxone® or an interferon [Betaseron® (or Extavia®), Rebif®, Avonex®] or 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), progesterone IUDs or other sex hormones during screening and during the 12-month study period.
  • 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, nonhormonal IUDs).
  • 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.
  • Greater than 130% or less than 80% of their ideal body weight based on Metropolitan Life Tables.
  • 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, cyclosporine, Tysabri.
  • Positive titers to HIV in the past.
  • Previous serious adverse effects with estrogen treatment.
  • Patients with MS-disease duration (since onset of symptoms) of greater than 15 years.
Female
18 Years to 50 Years
No
Contact: Jenny Bardens (310)206-2176 jbardens@mednet.ucla.edu
Contact: Janet Yau (310)794-4020 jyau@mednet.ucla.edu
United States
 
NCT01466114
11-002055
No
Rhonda Voskuhl, University of California, Los Angeles
University of California, Los Angeles
Synthetic Biologics (formerly Adeona Pharmaceuticals)
Principal Investigator: Rhonda Voskuhl, M.D. University of California, Los Angeles
University of California, Los Angeles
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP