Vaginal Estriol in Multiple Sclerosis

Dual Benefits of Vaginal Estriol: Improved Urogenital Health and Re-myelination in Relapsing Remitting Multiple Sclerosis (RRMS)

Study to evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms in female patients with RRMS. The secondary objective is to evaluate the potential role of vaginal estriol in re-myelination in RRMS patients.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Neurogenic Bladder
• Intervention / Treatment: Drug: vaginal estriol

Detailed Description

Pilot project to determine the effectiveness of 1 mg transvaginal estriol, as an adjunctive therapy for female MS patients. The goal is to recruit 20 patients from the MS clinic in the neurology department of Texas Tech University Health Sciences Center. This study has been planned in collaboration with reproductive endocrinology, endocrinology, gynecology and basic science. The 1mg transvaginal dose was chosen after careful search of the literature and consultation with collaborators.

Single-group pilot study.

Subjects:

Patients with relapsing remitting MS and urogenital symptoms (frequency, urgency, frequent urinary tract infections, incontinence) will be invited to participate in the study. Enrollment will be during their scheduled clinic appointment. Some candidates (patients of the primary investigator) may be contacted by phone and invited to participate in the study.

The clinical trial will be explained to potential participants in detail, reviewing the objectives and methodology of the study. There will be adequate time allotted to answer any questions or concerns from the potential participants. Those patients interested in participating in the study will be asked to sign the consent form. In order to remind patients about their follow-up visits, lab work, etc., they will be contacted routinely. Participants will be instructed to call in case of questions or concerns.

Patients will be evaluated clinically during their scheduled follow up in which a full neurological exam will be performed during each visit. Patients will be instructed by the primary investigator how to correctly use the vaginal cream. This will be done at their enrolment and reinforced by the principal investigator, during their follow up visits.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female patients with RRMS over the age of 40 to 65.

   • Being prescribed vaginal estriol to treat their urogenital symptoms such as frequency, urgency, incontinence and frequent urinary tract infections.
   • Patients that had underwent chemical or surgical hysterectomy.
2. Patients will continue their current disease modifying agent for MS during the trial.

Exclusion Criteria:

1. Patients with history of breast cancer, uterine or ovarian cancer.
2. Patients with progressive multiple sclerosis
3. Patients who are unable to undergo an MRI
4. Males
5. Patient is already on vaginal or oral or transdermal estrogens
6. Pregnant or breast-feeding patients
7. Patient taking sex hormones eg testosterone for libido
8. Patients taking DHEA or OTC related products that could influence the hormonal milieu.
9. Patient with prolapse uterus or conditions that would impact on transvaginal absorption of estriol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: urogenital symptoms; To evaluate the efficiency of vaginal estriol, as a treatment for urogenital symptoms in female patients with RRMS.	Drug: vaginal estriol; Estriol vaginal cream will be formulated by Twin Oaks specialty pharmacy-by the same compound specialist. 30 mg estriol powder will be mixed with 5 mL of propylene glycol and 22 g of vaginal base cream. The product can be stored at room temperature and has a shelf life of up to 4 months. It comes with an applicator.; Other Names: estriol cream
EXPERIMENTAL: remyelination; To evaluate the potential role of vaginal estriol in re-myelination in RRMS patients.	Drug: vaginal estriol; Estriol vaginal cream will be formulated by Twin Oaks specialty pharmacy-by the same compound specialist. 30 mg estriol powder will be mixed with 5 mL of propylene glycol and 22 g of vaginal base cream. The product can be stored at room temperature and has a shelf life of up to 4 months. It comes with an applicator.; Other Names: estriol cream

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bladder Control Scale (BLCS)	The questions are regarding control of the bladder, number of accidents in the past 4 weeks, alteration of activities because of bladder problems and restriction on lifestyle because of bladder problems. The total score for the BLCS is the sum of the scores for the 4 items. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Change from baseline at 9 months.	baseline and 9 months
Change in Visual Evoked Potential and Ocular Tomography Results From Baseline to 9 Months of Both Eyes	visual evoked potential measured in each eye at baseline and 9 months normal value should be bellow 100 milliseconds	Baseline and 9 months
Change in MS Quality of Life Questionnaire at Baseline and 9 Months. (Physical Score)	Multiple sclerosis quality of life questionnaire is an extensive questionnaire filled by the patient and graded by physician. It consists of 2 main areas the physical health which include physical function, health perceptions, energy fatigue, role limitations, pain, sexual function, social function and health distress. The mental health score which includes health distress, overall quality of life, emotional wellbeing, role limitations and cognitive function. The physical health and mental health parts each include a possible score range of 0-100. Overall the lower the score the better	Quality of life score at baseline and Quality of life score at 9 months

Collaborators and Investigators

• Sponsor: Texas Tech University Health Sciences Center
• Investigators: Principal Investigator: Mirla Avila, Texas Tech University

Publications and helpful links

General Publications

• Avila-Ornelas J, Avila M, Stosic M, Robles L, Prieto PG, Hutton GJ, Rivera VM. The role of postpartum intravenous corticosteroids in the prevention of relapses in multiple sclerosis. Int J MS Care. 2011 Summer;13(2):91-3. doi: 10.7224/1537-2073-13.2.91.
• Cody JD, Jacobs ML, Richardson K, Moehrer B, Hextall A. Oestrogen therapy for urinary incontinence in post-menopausal women. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD001405. doi: 10.1002/14651858.CD001405.pub3.
• Harlow DE, Honce JM, Miravalle AA. Remyelination Therapy in Multiple Sclerosis. Front Neurol. 2015 Dec 10;6:257. doi: 10.3389/fneur.2015.00257. eCollection 2015.
• Mallik S, Samson RS, Wheeler-Kingshott CA, Miller DH. Imaging outcomes for trials of remyelination in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014 Dec;85(12):1396-404. doi: 10.1136/jnnp-2014-307650. Epub 2014 Apr 25.
• Moore KH. The costs of urinary incontinence. Med J Aust. 2001 May 7;174(9):436-7. doi: 10.5694/j.1326-5377.2001.tb143368.x. No abstract available.
• Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, Olivera CK, Abed H, Balk EM, Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1147-1156. doi: 10.1097/AOG.0000000000000526.
• Tiwari-Woodruff S, Voskuhl RR. Neuroprotective and anti-inflammatory effects of estrogen receptor ligand treatment in mice. J Neurol Sci. 2009 Nov 15;286(1-2):81-5. doi: 10.1016/j.jns.2009.04.023. Epub 2009 May 13.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 20, 2019
• Primary Completion (ACTUAL): November 10, 2020
• Study Completion (ACTUAL): November 29, 2020

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 10, 2018
• First Posted (ACTUAL): December 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 21, 2022
• Last Update Submitted That Met QC Criteria: August 25, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: multiple sclerosis; remyelination; urogenital health
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Multiple Sclerosis; Sclerosis; Urinary Bladder, Neurogenic
• Other Study ID Numbers: L19-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes