Study of Oxytocin to Treat Vaginal Atrophy in Postmenopausal Women

This study has been completed.
Sponsor:
Information provided by:
PeP-Tonic Medical AB
ClinicalTrials.gov Identifier:
NCT01432470
First received: August 16, 2010
Last updated: September 12, 2011
Last verified: September 2011
  Purpose

Up to 50% of all postmenopausal women, experience vaginal dryness, irritation, burning, itching or discomfort, which often make sex to become difficult or painful. These symptoms combined are known as vaginal atrophy. Vaginal atrophy is a consequence of the lining tissue of the vagina becoming thinner, drier, and less elastic due to the lack of estrogen. In addition, vaginal atrophy is associated with an increased pH, which creates an environment more susceptible to infections. The mucosal epithelium shows signs of severe atrophy and cytological examination demonstrate increased number of the basal and parabasal cells and reduced number of superficial cells.

Estrogen treatment either as hormone replacement therapy or topical application is a common treatment for vaginal atrophy. However, some women experience adverse reactions such as uterine bleeding, perineal pain and breast pain and many women are also reluctant to use estrogens due to a general negative view to this topic in the society.

Oxytocin is a peptide hormone, which is normally released into the circulation via the pituitary. The most well known effects of oxytocin are its roles in female reproduction such as facilitation of birth and breast feeding. In addition, oxytocin has in vitro been shown to exert positive effects on the proliferation of human vaginal mucosal cells from postmenopausal women.

Considering the stimulatory effects of oxytocin on vaginal mucosal cell proliferation, topical application of oxytocin to the vaginal mucosa may be an approach to treat vaginal atrophy. In one previous placebo-controlled study on 20 postmenopausal women suffering from vaginal atrophy, a gel containing oxytocin for topical intra-vaginal administration was applied daily for seven days. The results indicated that for subjects receiving topical oxytocin the vaginal atrophy assessed by histological examination was reversed after treatment. A similar effect was not seen in the placebo group, which indicated a difference between placebo and active treatment. However, the limited number of exposed subjects in this pilot study necessitates a larger study in order to generate conclusive proof of concept data for the effects of oxytocin on vaginal atrophy.

Due to the limitations of estrogens in the treatment of vaginal atrophy, many postmenopausal women are left without an effective remedy. Hence, there is a need for alternative non-estrogenic treatments of this indication. The present study is aiming to investigate the efficacy of topical oxytocin in the treatment of vaginal atrophy.

The main objective of this study is to investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo.


Condition Intervention Phase
Postmenopause
Vaginal Atrophy
Drug: Oxytocin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Placebo Controlled Multi-centre Study to Evaluate the Effects of Topical Oxytocin on Vaginal Atrophy in Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by PeP-Tonic Medical AB:

Primary Outcome Measures:
  • The Maturation Value (MV) [ Time Frame: 12 weeks of oxytocin treatment as compared to placebo ] [ Designated as safety issue: No ]
    The MV describes the change in percentage of superficial cells (Meisels A. The Maturation Value. Acta Cytol. 1967, Jul-Aug;11(4):249)


Secondary Outcome Measures:
  • Vaginal Atrophy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Atrophy in histological biopsies is assessed by a 4-grade scale

  • Quality of Life [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: No ]
    Using a standardized QoL form

  • The Maturation Value [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    Same as primary outcome but after 2 weeks treatment

  • Vaginal pH [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: No ]
  • Concentration of Oxytocin in serum [ Time Frame: 0-60 min after drug admin. ] [ Designated as safety issue: Yes ]
    The purpose of the evaluation is only to evaluate the systemic uptake. No other PK variables than the concentration are calculated.

  • Clinician evaluation of vaginal mucosal appearance [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: No ]
    Evaluation of seven different features, where every feature is assessed by a 4-grade scale.

  • Laboratory assessments [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: Yes ]
    Clinical Chemistry, Haematology, Urine analysis, Cervical cytology,Endometrial Histology

  • Concentration of 17 beta-estradiol in serum [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Vital signs [ Time Frame: 2 and 12 weeks ] [ Designated as safety issue: Yes ]
    Heart rate and blood pressure


Estimated Enrollment: 74
Study Start Date: August 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxytocin, Intravaginal administration Drug: Oxytocin
Gel for intravaginal use, 600 IU once per day for 2 weeks followed by 600 IU twice a week for ten weeks
Placebo Comparator: Placebo, Intravaginal administration Drug: Placebo
Gel for intravaginal use of identical appearance as active substance, once per day for two weeks followed by twice a week for ten weeks

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed Informed Consent
  • at least 40 years of age
  • naturally postmenopausal women, completely without menstrual bleedings for at least four years prior to screening.
  • FSH plasma levels at least 40 IU/L and 17β-estradiol levels less than 70pmol/L
  • Vaginal pH more than 5.0
  • BMI at most 29 kg/m2
  • Vaginal atrophy verified by cytological assessment of the vaginal mucosal epithelium. Vaginal atrophy is defined as at most 5% of superficial cells.

Exclusion Criteria:

  • Usage of any sex steroids including phytoestrogens, hormonal intra-uterine device or herbal medicinal products with known estrogenic effects within 3 months prior to screening.
  • Usage of any lubricant for intra-vaginal administration at inclusion
  • Any condition that is a contraindication to treatment with sex steroids
  • Vaginal bleeding of unknown origin
  • Any untreated urogenital infection within 7 days prior to inclusion
  • Any prior or concurrent malignant disease or endometrial hyperplasia
  • Cervical cytology at least CIN 1 assessed during screening
  • Clinically significant medical history (excluding medically well-controlled hypertension and hypercholesterolemia), findings from physical examinations, vital signs, cytology, histology or laboratory analyses that may interfere with the study objectives or compromise the safety of the subject as judged by the Investigator.
  • Systolic Blood Pressure at least 140 mmHg or Diastolic Blood Pressure at least 90 mmHg at screening
  • Participation in any other interventional clinical trial within 3 months prior to screening
  • Known or suspected drug or alcohol abuse, within 12 months prior to screening
  • Concurrent and diagnosed nephrologic or hepatic disorder
  • Diagnosed with HIV, Hepatitis B or C
  • Known or suspected allergy to any ingredient of the study product
  • Incapacity to perform study procedures, as judged by the Investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432470

Locations
Sweden
Karolinska University Hospital-Huddinge
Huddinge, Sweden, SE-141 86
Uppsala University Hospital
Uppsala, Sweden, SE-751 85
United Kingdom
Northwick Park & St Marks Hospital NHS Trust
Harrow Middlesex, United Kingdom, HA1 3UJ
Sponsors and Collaborators
PeP-Tonic Medical AB
  More Information

No publications provided

Responsible Party: Dan Markusson, PeP-Tonic Medical AB
ClinicalTrials.gov Identifier: NCT01432470     History of Changes
Other Study ID Numbers: OxyPeP-001
Study First Received: August 16, 2010
Last Updated: September 12, 2011
Health Authority: Sweden:Medical Product Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by PeP-Tonic Medical AB:
vaginal atrophy

Additional relevant MeSH terms:
Atrophy
Pathological Conditions, Anatomical
Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014