DHEA Bioavailability Following Administration of Vaginal Suppositories in Post-Menopausal Women With Vaginal Atrophy

DHEA Bioavailability Following Administration of Vaginal Suppositories in Post-Menopausal Women With Vaginal Atrophy-Phase I Randomized,Placebo-Controlled, Double-Blind Study.

The purpose of the study is to evaluate the systemic bioavailability of DHEA and its metabolites and the pharmacokinetics of vaginal suppositories at four different DHEA concentration.

Study Overview

• Status: Completed
• Conditions: Vaginal Atrophy
• Intervention / Treatment: Drug: Placebo; Drug: DHEA

Detailed Description

Humans, are unique among animal species in having adrenals that secrete large amounts of the inactive precursor steroids dehydroepiandrosterone (DHEA) and especially its sulfate DHEA-S. The marked reduction in the formation of DHEA-S by the adrenals during aging results in a dramatic fall in the formation of androgens and estrogens in peripheral target tissues, a situation that has been proposed to be associated with age-related diseases including skin atrophy, insulin resistance and obesity. Much attention has been given to the benefits of DHEA administered to postmenopausal women, especially on the bone, skin, vagina and well being after oral as well as percutaneous administration of the precursor steroid.

Therefore, this study proposes to evaluate the systemic bioavailability and the effectiveness of 1.3 mL vaginal suppositories of DHEA at 4 different concentrations (0.0%, 0.5%, 1.0% et 1.8%) following 1 week administration of vaginal suppositories in post-menopausal women with vaginal atrophy. This is a phase I, randomized, placebo-controlled, double-blind study.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G2
    • Clinique des traitements hormonaux CHUL Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women,
• Experiencing one symptom of vaginal atrophy (vaginal dryness, vaginal and/or vulvar irritation/itching, dysuria, vaginal pain associated with sexual activity or vaginal bleeding associated with sexual activity,
• Women having a low maturation index and a vaginal pH above 5,
• Endometrial thickness of 4 mm or less at transvaginal ultrasonography,
• Body weight within 18.5 and 32.0 according to body mass index.

Exclusion Criteria:

• Undiagnosed abnormal genital bleeding,
• Active or history of thromboembolic disease,
• Significant metabolic or endocrine disease,
• Significant complication on previous hormonal therapy,
• Use of hormonal implants within 6 months prior to study entry,
• Use of oral estrogen, progestin or DHEA in the 8 weeks prior to baseline,
• Use of natural (phytoestrogens) or herbal products in the 2 weeks prior to baseline,
• Chronic use of corticosteroids,
• Hypertension not controlled by standard therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo suppository; once daily for 7 days.	Drug: Placebo; Placebo
Experimental: DHEA 0.50%; DHEA 0.50% (6.5 mg) suppository; once daily for 7 days.	Drug: DHEA; DHEA; Other Names: dehydroepiandrosterone; prasterone
Experimental: DHEA 1.0%; DHEA 1.0% (13 mg) suppository; once daily for 7 days.	Drug: DHEA; DHEA; Other Names: dehydroepiandrosterone; prasterone
Experimental: DHEA 1.8%; DHEA 1.8% (23.4 mg) suppository; once daily for 7 days.	Drug: DHEA; DHEA; Other Names: dehydroepiandrosterone; prasterone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The evaluation of the systemic bioavailability of DHEA and its metabolites.	Day 1-2 and Day 7-8
The pharmacokinetics of vaginal suppositories at four different DHEA concentrations.	Day 1-2 and Day 7-8

Secondary Outcome Measures

Outcome Measure	Time Frame
The safety and tolerance of the suppositories.	Day 1 to Day 8 (plus follow-up of Adverse Events for 30 days after last dose)
The effect of treatment on maturation index and value	Day 7

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Investigators: Study Chair: Fernand Labrie, MD, Ph D, CHUL Research Center Director; Principal Investigator: Cusan Leonello, MD Ph D, CHUL Research Center

Publications and helpful links

General Publications

• Labrie F, Cusan L, Gomez JL, Cote I, Berube R, Belanger P, Martel C, Labrie C. Effect of intravaginal DHEA on serum DHEA and eleven of its metabolites in postmenopausal women. J Steroid Biochem Mol Biol. 2008 Sep;111(3-5):178-94. doi: 10.1016/j.jsbmb.2008.06.003. Epub 2008 Jun 12. Erratum In: J Steroid Biochem Mol Biol. 2008 Nov;112(1-3):169.
• Labrie F, Martel C, Berube R, Cote I, Labrie C, Cusan L, Gomez JL. Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens. J Steroid Biochem Mol Biol. 2013 Nov;138:359-67. doi: 10.1016/j.jsbmb.2013.08.002. Epub 2013 Aug 14.
• Labrie F, Martel C. A low dose (6.5 mg) of intravaginal DHEA permits a strictly local action while maintaining all serum estrogens or androgens as well as their metabolites within normal values. Horm Mol Biol Clin Investig. 2017 Feb 1;29(2):39-60. doi: 10.1515/hmbci-2016-0042.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: January 31, 2007
• First Submitted That Met QC Criteria: January 31, 2007
• First Posted (Estimate): February 1, 2007

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: April 6, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: DHEA; Prasterone; Menopause; Vaginal atrophy
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Dehydroepiandrosterone
• Other Study ID Numbers: ERC-213

Plan for Individual participant data (IPD)

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