A Phase 2 interventional study of Estriol and Placebo in Relapsing Remitting Multiple Sclerosis, sponsored by University of California, Los Angeles. Completed at 16 sites in 2 countries. Open to female participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2016-06-16.
Sponsored by University of California, Los Angeles · Phase 2, Interventional, and Treatment
This is a double-blinded, placebo controlled study of estriol pills versus placebo pills in relapsing remitting multiple sclerosis. The study treatment will be an added on to Copaxone injections in all subjects. The primary outcome measure is a reduction in relapses.
Multiple sclerosis (MS) relapses are known to be significantly decreased during pregnancy. This proposal will establish whether oral treatment with estriol, the major estrogen of pregnancy, induces a decrease in relapses in relapsing remitting multiple sclerosis (RRMS) subjects when used in combination with injectable Copaxone. Previously, in a pilot study, it has been demonstrated that treatment of RRMS subjects with oral estriol for six months resulted in a significant reduction in gadolinium enhancing lesions on serial brain MRIs (Annals of Neurology, 2002; 52:421-428) and caused a favorable shift in immune responses (Journal of Immunology, 2003; 171:6267-6274). This is an add-on study aiming to extend these previous findings by treating longer and focusing on clinical outcomes. The combination of Copaxone injection plus estriol pill (8 mg per day) will be compared to Copaxone injection plus placebo pill in a double blind trial. The duration of treatment will be two years and the primary outcome measure will be relapse rate. Other outcomes will include disability measures and brain MRI outcomes. Safety measures (blood tests and gynecologic evaluations) will also be followed and correlations will be made between serum estriol levels with efficacy and safety. The overall goal of this study will be the development of a new oral treatment, estriol, for RRMS.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
This study's enrollment of 158 is above the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →University of California, Los Angeles is the lead sponsor of 1,142 studies on the registry; 192 are open to participants now.
Of its 91 completed or terminated interventional studies of FDA-regulated products, 66 (73%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Estriol Capsules (daily) plus Copaxone injections (daily). Progestin capsules given for 2 weeks every 3 months to avoid unopposed estrogens.
Drug: Estriol · Drug: Copaxone
Placebo Capsules (daily) plus Copaxone injections (daily). A second placebo capsule given for 2 weeks every 3 months.
Drug: Placebo · Drug: Copaxone
Estriol 8 mg capsule, once per day, duration of treatment is 2 years
Also known as: E3, estrogen
Placebo capsule, once a day, treatment duration is 2 years
Also known as: "sugar pill"
Injection, once a day, all subjects
Also known as: glatiramer acetate
Confirmed Relapse, Annualized Relapse Rate
A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.
Time frame: 24 months
Relapse Event, Annualized Relapse Rate
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
Time frame: 24 months
Confirmed Relapse, Probability of First Relapse
Time frame: 24 months
Relapse Event, Probability of First Relapse Event
Time frame: 24 months
Confirmed Relapse, Annualized Relapse Rate
A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.
Time frame: 12 months
Relapse Event, Annualized Relapse Rate
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
Time frame: 12 months
| Milestone | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Started | 82 | 76 |
| Completed | 60 | 56 |
| Not completed | 22 | 20 |
| Withdrew: Adverse event | 4 | 6 |
| Withdrew: Lack of efficacy | 4 | 4 |
| Withdrew: Lost to follow-up | 4 | 4 |
| Withdrew: Protocol violation | 1 | 0 |
| Withdrew: Patient refusal | 8 | 4 |
| Withdrew: Other | 1 | 2 |
A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.
| relapses per year | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Confirmed Relapse, Annualized Relapse Rate | 0.25 (0.17 to 0.37) | 0.37 (0.25 to 0.53) |
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
| relapses per year | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Relapse Event, Annualized Relapse Rate | 0.32 (0.22 to 0.46) | 0.46 (0.32 to 0.65) |
| probability of relapse at 24 months | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Confirmed Relapse, Probability of First Relapse | 33.3 (23.8 to 45.4) | 42.9 (32.1 to 55.5) |
| probability of relapse event at 24 mo | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Relapse Event, Probability of First Relapse Event | 40.5 (30.0 to 53.0) | 46.9 (35.9 to 59.3) |
A confirmed relapse was defined as new neurological symptoms or worsening of pre-existing symptoms, lasting at least 48 hours in a subject who had been neurologically stable or improving in the previous 30 days, accompanied by objective change in the neurological examination (worsening of 0.5 points on the EDSS or worsening by 1.0 or more points on the pyramidal, cerebellar, brainstem or visual functional system scores), not due to fatigue alone and not associated with fever or infection.
| relapses per year | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Confirmed Relapse, Annualized Relapse Rate | 0.25 (0.16 to 0.40) | 0.48 (0.33 to 0.69) |
Met all criteria for relapse except not confirmed to have increase in EDSS by an independent examiner.
| relapses per year | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Relapse Event, Annualized Relapse Rate | 0.33 (0.22 to 0.50) | 0.61 (0.44 to 0.84) |
Collected over After enrollment, during the 24-month treatment period. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Estriol Capsules Plus Copaxone Injections | — | 8/82 (9.8%) | 76/82 (92.7%) |
| Placebo Capsules Plus Copaxone Injections | — | 10/76 (13.2%) | 67/76 (88.2%) |
| Event | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| MS Relapse (hospitalization)Nervous system disorders | 2/82 | 5/76 |
| PregnancyPregnancy, puerperium and perinatal conditions | 2/82 | 0/76 |
| Urinary Tract InfectionInfections and infestations | 1/82 | 1/76 |
| Accidentally took other's drugInvestigations | 0/82 | 1/76 |
| Acute appendicitisInfections and infestations | 0/82 | 1/76 |
| B-cell lymphomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/82 | 1/76 |
| car accident related body numbnessInjury, poisoning and procedural complications | 0/82 | 1/76 |
| Right Knee ReplacemebtMusculoskeletal and connective tissue disorders | 0/82 | 1/76 |
| Migraine headache related eye painEye disorders | 1/82 | 0/76 |
| Heart Failure/ pace maker implantationCardiac disorders | 1/82 | 0/76 |
| Event | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections |
|---|---|---|
| Uterus, endometrial thickness > 8mm (ultrasound)Reproductive system and breast disorders | 24/82 | 27/76 |
| Upper respiratory InfectionInfections and infestations | 22/82 | 26/76 |
| GA injection area abnormalitiesSkin and subcutaneous tissue disorders | 21/82 | 12/76 |
| Irregular menses/ spottingReproductive system and breast disorders | 19/82 | 3/76 |
| Urinary tract infectionRenal and urinary disorders | 15/82 | 10/76 |
| FatigueGeneral disorders | 13/82 | 8/76 |
| Depression/ AnxietyPsychiatric disorders | 12/82 | 9/76 |
| HeadacheGeneral disorders | 9/82 | 11/76 |
| Menstrual flow amount increasedReproductive system and breast disorders | 11/82 | 6/76 |
| SinusitisRespiratory, thoracic and mediastinal disorders | 6/82 | 10/76 |
Relapsing remitting multiple sclerosis women aged 18 to 50 years.
| Age, Categorical(Participants) | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 82 | 76 | 158 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections | Total |
|---|---|---|---|
| Mean | 37.7 ± 7.6 | 37.1 ± 7.3 | 37.4 ± 7.45 |
| Sex: Female, Male(Participants) | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections | Total |
|---|---|---|---|
| Female | 82 | 76 | 158 |
| Male | 0 | 0 | 0 |
| Region of Enrollment(participants) | Estriol Capsules Plus Copaxone Injections | Placebo Capsules Plus Copaxone Injections | Total |
|---|---|---|---|
| United States | 82 | 76 | 158 |
Plan to share: Yes — Investigators interested in further research using the data should contact Dr. Voskuhl with proposed plans and request.
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University of California, Los Angeles