Estriol Treatment in Multiple Sclerosis (MS): 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.
Relapsing-remitting Multiple Sclerosis
Secondary-progressive Multiple Sclerosis
Primary-progressive Multiple Sclerosis
Other: Progestin Placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Double-Blind, Placebo Controlled Trial of Estriol Treatment in Women With Multiple Sclerosis: Effect on Cognition.|
- 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.
- 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 MRI measurements of whole brain volume, T2 lesion volume and number of enhancing lesions. [ 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.
- 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.
|Study Start Date:||October 2011|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Experimental: Group A: Estriol
Standard MS Treatment + Estriol
2 capsules of 2 mg (total of 8 mg) PO QD
Other Name: SynapauseDrug: 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
Placebo Comparator: Group B: Placebo
Standard MS Treatment + Placebo
4 capsules PO QDOther: 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.
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 BG-12).
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.
|Contact: Jenny Bardens||(310)firstname.lastname@example.org|
|Contact: Janet Yau||(310)email@example.com|
|United States, California|
|University of California Los Angeles||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Janet Yau, BS 310-794-4020 firstname.lastname@example.org|
|Contact: Jenny Bardens, RN (310) 206-2176 email@example.com|
|Sub-Investigator: Barbara Giesser, MD|
|Sub-Investigator: Callene Momtazee, MD|
|United States, Colorado|
|The University of Colorado Denver||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Barbetta Halliday 303-724-4717 firstname.lastname@example.org|
|Contact: Haley Steinert (303) 724-4172 email@example.com|
|Principal Investigator: John R Corboy, M.D.|
|United States, New Mexico|
|The University of New Mexico||Not yet recruiting|
|Albuquerque, New Mexico, United States, 87131|
|Contact: Lori Bachert 505-272-8905 Lbachert@salud.unm.edu|
|Principal Investigator: Corey Ford, M.D.|
|United States, Pennsylvania|
|The University of Pennsylvania||Not yet recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Vanessa Zimmerman 215-349-5162 Vanessa.Zimmerman@uphs.upenn.edu|
|Principal Investigator: Dina Jacobs, M.D.|
|Principal Investigator:||Rhonda Voskuhl, M.D.||University of California, Los Angeles|