Dose-relationship of Vaginally Administrated Oxytocin in Postmenopausal Women (OXYPEP002)

A Double-blind, Placebo Controlled Single Centre Trial to Evaluate the Dose-relationship of the Effects of Vaginally Administered Oxytocin on the Vaginal Mucosal Membrane in Postmenopausal Women With Vaginal Atrophy

Up to 50% of all postmenopausal women, experience vaginal drynes, i.e. vaginal atrophy is a consequence 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 senile atrophy and cytological examination demonstrate increased number of the basal and parabasal cells and reduced number of superficial cells . Unlike some other menopausal symptoms (for instance hot flushes), vaginal symptoms generally persist or worsen with aging.Oxytocin is a peptide hormone and it is released systemically via the posterior pituitary. The most well known effects of oxytocin are its roles in female reproduction such as facilitation of birth and breast feeding. Oxytocin has also shown to exert positive effects on the proliferation of human vaginal mucosal cells from postmenopausal women, an effect which could be attributed either to the direct stimulation of new cell formation or to an increased production of other growth factors. The primary objective is to investigate the dose relationsship of topical administrated Vagitocin on the vaginal mucosal membrane, measured in the change (%)of superficial cells up to 7 weeks after baseline.

Study Overview

• Status: Completed
• Conditions: Vaginal Atrophy
• Intervention / Treatment: Drug: Placebo; Drug: Oxytocin 100 i.u.; Drug: Oxytocin 400 i.u.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Huddinge
    • Stockholm, Huddinge, Sweden, 14186
      • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Naturally postmenopausal or ooforectomized women, completely without menstrual bleedings for at least four years prior to baseline.
2. > 40 years of age.
3. Moderate to severe symptoms of at least one of the following criteria of vulvar and vaginal atrophy associated with the menopause, according to the patient's self-assessement: vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity, or presence of vaginal bleeding associated with sexual activity.
4. Atrophic mucosa according to the investigator's assessment.
5. Signed Informed Consent.

Exclusion Criteria:

• 1. Usage of any sex steroids including phytoestrogens, hormonal intra-uterine device or herbal medicinal products with known estrogenic effects within 3 months prior to baseline.

  2. Usage of any lubricant for intra-vaginal administration at baseline. 3. Vaginal bleeding of unknown origin. 4. Vaginal pH ≤ 5.0. 5. Any ongoing uro-genital infection within 7 days prior to baseline. 6. Body Mass Index (BMI) >30 kg/m2. 7. Systolic Blood Pressure > 150 mmHg and Diastolic Blood Pressure > 90 mmHg at baseline.

  8. Any concurrent known or suspected tumor disease as judged by the investigator.

  9. Clinically significant medical history (excluding medically well-controlled hypertension and hypercholesterolemia), abnormal findings from physical examinations, vital signs, cytology, histology, US examination of uterus and ovaries or laboratory analyses that may interfere with the trial objectives or compromise the safety of the patient as judged by the Investigator.

  10. Concurrent and diagnosed nephrological or hepatic disorder 11. Diagnosed with HIV, Hepatitis B or C 12. Known or suspected drug or alcohol abuse, within 12 months prior to baseline.

  13. Known or suspected allergy to any ingredient of the trial product. 14. Incapacity to perform trial procedures, as judged by the investigator. 15. Participation in any other interventional clinical trial within 3 months prior to baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxytocin 100 i.u.; N=24 patients are administrated Oxytocin 100 i.u. vaginally	Drug: Oxytocin 100 i.u.; Other Names: Vagoticin
Experimental: Oxytocin 400 i.u.; N=24 patients are administrated Oxytocin 400 i.u. vaginally	Drug: Oxytocin 400 i.u.; Other Names: Vagoticin
Placebo Comparator: Placebo; N=16 patients are administrated placebo vaginally	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the dose-relationship of topical Vagitocin on the vaginal mucosal membrane.	Change in percentage points of superficial cells from baseline visit (visit 1) to 7 weeks of treatment (Visit 3).	from baseline visit to 7 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the safety and tolerability of topical Vagitocin treatment.	Change in percentage points of superficial cells from baseline visit to 2 (Visit 2) weeks of treatment. Change in maturation value from baseline visit to 2 (Visit 2) and 7 (Visit 3) weeks of treatment. Change in vaginal pH from baseline visit to 2 (Visit 2) and 7 (Visit 3) weeks of treatment. Visual appearance of the vaginal mucosa after 2 (Visit 2) and 7 (Visit 3) weeks of treatment; Patients´ self-assessment of the most bothersome symptomafter 2 (Visit 2), 7 (Visit 3), weeks of treatment and at the telephone follow-up after 9 weeks.; Histological assessment after 2 (Visit 2) and 7 weeks (Visit 3) of treatment.; Change in score in selected items of WHQ/SSP from baseline visit to 7 (Visit 3) weeks of treatment and at the telephone follow-up after 9 weeks.	From visit 2 to visit 7

Collaborators and Investigators

• Sponsor: PepTonic Medical AB
• Collaborators: Pharma Consulting Group AB
• Investigators: Principal Investigator: Aino F Jonasson, M.D, PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: November 13, 2013
• First Submitted That Met QC Criteria: November 13, 2013
• First Posted (Estimate): November 19, 2013

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 10, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: OXYPEP002