Clinical trial NCT00429806: DHEA Bioavailability Following Administration of Vaginal Suppositories in Post-Menopausal Women With Vaginal Atrophy
Official title: DHEA Bioavailability Following Administration of Vaginal Suppositories in Post-Menopausal Women With Vaginal Atrophy-Phase I Randomized,Placebo-Controlled, Double-Blind Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Vaginal Atrophy
Keywords: Vaginal atrophy
DHEA
Prasterone
Menopause
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
First posted: 2007-02-01
Enrollment: 40
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The evaluation of the systemic bioavailability of DHEA and its metabolites.
timeFrame: Day 1-2 and Day 7-8
measure: The pharmacokinetics of vaginal suppositories at four different DHEA concentrations.
timeFrame: Day 1-2 and Day 7-8
Secondary outcomes:
measure: The safety and tolerance of the suppositories.
timeFrame: Day 1 to Day 8 (plus follow-up of Adverse Events for 30 days after last dose)
measure: The effect of treatment on maturation index and value
timeFrame: Day 7
Other outcomes:
Locations:
city: Quebec
country: Canada
facility: Clinique des traitements hormonaux CHUL Research Center
Study officials:
affiliation: CHUL Research Center Director
name: Fernand Labrie, MD, Ph D
role: STUDY_CHAIR
affiliation: CHUL Research Center
name: Cusan Leonello, MD Ph D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.