Primary Ovarian Insufficiency: Phenotype and Optimal Treatment

NCT03568708 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: FP00000706
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study will observe the progression of newly diagnosed POI patients physical and psychology outcomes after initiating standard of care HRT treatment in comparison to healthy female control participants' physical and psychology health over 24 months.

Conditions

Primary Ovarian Insufficiency

Keywords

Primary Ovarian Insufficiency; Hormone Replacement Therapy; Estrogen Deficiency

Outcome Measures

Primary Outcomes (1)

• Change in Dual Energy X-ray Absorptiometry (DXA) Measure of Bone Mineral Density (BMD) of the Lumbar Spine

  Change in height adjusted areal BMD Z-score of the lumbar spine from baseline to 24 months within groups. BMI Z-score, calcium intake, vitamin D intake and physical activity were included in the analysis. As DXA BMD Z-scores already include race, age, and sex, these variables were not included in the analysis. Z-scores ranging between -2.0 and 2.0 are considered normal. A Z-score \<-2.0 is considered low. This analysis considers change in Z-score, therefore a high value reflects a greater increase in BMD Z-score.

  Change in bone mineral density and body composition from baseline to 24 months

Secondary Outcomes (10)

• Change in Dual Energy X-ray Absorptiometry (DXA) Measure of Bone Mineral Density (BMD) at the Whole Body Less Head, Total Hip, and Femoral Neck

  baseline to 24 months

• Change in Volumetric Bone Mineral Density (vBMD) at the Distal Radius as Measured by Peripheral Quantitative Computed Tomography (pQCT)

  Change from baseline to 24 months

• Anthropometrics

  Baseline and 24 months

• Change in Lean Mass as Measured by DXA Body Composition

  Change in lean mass from baseline to 24 months

• Change in Symptoms of Anxiety as Measured by Screen for Child Anxiety Related Disorders (SCARED)

  Change from SCARED score baseline to 24 months

Study Arms (2)

Control Participants

NO INTERVENTION

The control group will reflect a comparison group similar to the POI patient group. As bone density, body composition, and cognitive domains continue to mature throughout the teenage years, this comparison group will provide an important metric of normal growth and development.

POI Participants

EXPERIMENTAL

This group will be participants who have been recently diagnosed with POI. In an open-label fashion, participants with POI will receive Transdermal Estrogen(beginning at a dose of 25 μg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch).

Drug: Transdermal Estrogen

Interventions

Transdermal Estrogen DRUG

In an open-label fashion, participants with POI will receive transdermal estradiol (beginning at a dose of 25 µg/patch applied weekly), with the dose increased at 3, 6 12, and 18 months (to 37.5, 50, 75, and 100 µg/patch).

Also known as: Estradiol-estradiol patch

POI Participants

Eligibility Criteria

• Age: 11 Years - 18 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The participant must:
• Be willing to give informed consent/assent
• Have a diagnosis of POI based on 2 elevated serum follicle stimulating hormone (FSH) levels obtained \>1 month apart.
• Be English-speaking

You may not qualify if:

• The participant must not:
• Have other chronic disease known to affect bone health (e.g., cystic fibrosis, celiac disease, etc.)
• Have an identified secondary cause of ovarian insufficiency
• Have POI in the setting of Turner syndrome, Fanconi Anemia, galactosemia, or Perrault syndrome (as associated neurological/medical sequelae could confound baseline measures)
• Have used medications known to affect bone metabolism over previous 3 months (e.g. anticonvulsants, chronic use of glucocorticoids, Depo-Provera, oral contraceptive pills)
• Be currently pregnant (to be confirmed by pregnancy testing)
• The participant must:
• Be similar in age and race group to the idiopathic POI group
• Control participants age must be within one year of age from the POI participant at the time of enrollment. Age may be within one year older or one year younger
• Race of controls participants will be matched based on race of POI patient participants
• Have a BMI within 20% of the BMI of the case-matched participant
• If postmenarchal, will be regularly menstruating (cycles between 21-35 days)
• a. if POI participant is \<12.5yrs (mean age of menarche) will match with a pre- menarchal control participant
• Be English-speaking
• The participant must not:

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Patty Brisben Foundation For Women's Sexual Health: collaborator

Study Sites (1)

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Related Publications (8)

• Gordon CM, Kanaoka T, Nelson LM. Update on primary ovarian insufficiency in adolescents. Curr Opin Pediatr. 2015 Aug;27(4):511-9. doi: 10.1097/MOP.0000000000000236.

  PMID: 26087426 BACKGROUND

• Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009 Feb 5;360(6):606-14. doi: 10.1056/NEJMcp0808697.

  PMID: 19196677 BACKGROUND

• Committee opinion no. 605: primary ovarian insufficiency in adolescents and young women. Obstet Gynecol. 2014 Jul;124(1):193-197. doi: 10.1097/01.AOG.0000451757.51964.98.

  PMID: 24945456 BACKGROUND

• Sadeghi MR. New hopes for the treatment of primary ovarian insufficiency/premature ovarian failure. J Reprod Infertil. 2013 Jan;14(1):1-2. No abstract available.

  PMID: 23926553 BACKGROUND

• Gordon CM, Zemel BS, Wren TA, Leonard MB, Bachrach LK, Rauch F, Gilsanz V, Rosen CJ, Winer KK. The Determinants of Peak Bone Mass. J Pediatr. 2017 Jan;180:261-269. doi: 10.1016/j.jpeds.2016.09.056. Epub 2016 Nov 3. No abstract available.

  PMID: 27816219 BACKGROUND

• Bakhsh H, Dei M, Bucciantini S, Balzi D, Bruni V. Premature ovarian insufficiency in young girls: repercussions on uterine volume and bone mineral density. Gynecol Endocrinol. 2015 Jan;31(1):65-9. doi: 10.3109/09513590.2014.958987. Epub 2014 Sep 9.

  PMID: 25203144 BACKGROUND

• Popat VB, Calis KA, Vanderhoof VH, Cizza G, Reynolds JC, Sebring N, Troendle JF, Nelson LM. Bone mineral density in estrogen-deficient young women. J Clin Endocrinol Metab. 2009 Jul;94(7):2277-83. doi: 10.1210/jc.2008-1878. Epub 2009 Apr 28.

  PMID: 19401379 BACKGROUND

• Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, Frederick MM, Huang X, Lu M, Mahboubi S, Hangartner T, Winer KK. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab. 2011 Oct;96(10):3160-9. doi: 10.1210/jc.2011-1111. Epub 2011 Sep 14.

  PMID: 21917867 RESULT

MeSH Terms

Conditions

Primary Ovarian Insufficiency

Interventions

Ortho Evra

Condition Hierarchy (Ancestors)

Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Results Point of Contact

• Title: Dr. Halley Wasserman
• Organization: CIncinnati Children's Hospital Medical Center

halley.wasserman@cchmc.org

513-803-3815

Study Officials

• Catherine Gordon, MD,Msc

  Boston Children's Hospital and Cincinnati Children's Hospital Medical Center

  PRINCIPAL INVESTIGATOR

• Halley Wasserman, MD, MSc

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Division of Endocrinology, University of Cincinnati Department of Pediatrics

Study Record Dates

• First Submitted: May 11, 2018
• First Posted: June 26, 2018
• Study Start: November 1, 2018
• Primary Completion: January 5, 2023
• Study Completion: January 5, 2023
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)