Use of Pulsatile Intravenous FSH to Mitigate Reprometabolic Syndrome

NCT06414096 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 23-2564b
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: The investigators hypothesize that pulsatile FSH intravenous administration to women with obesity will correct the Reprometabolic Syndrome (RMS) luteal deficiency phenotype. Specific Aim: To test the hypothesis that pulsatile IV administration of FSH will rescue the impaired folliculogenesis and relative hypogonadotropic hypogonadism, characteristic of obesity. The investigators will accomplish this by administering a cycle of pulsatile FSH to women with obesity and comparing their hormone output to a cycle using conventional, daily FSH injection at the identical daily dose. The primary outcome will be luteal phase progesterone excretion.

Conditions

Infertility; Obesity

Outcome Measures

Primary Outcomes (1)

• Urinary Pdg concentration

  The primary endpoint of the study is luteal progesterone metabolite (pregnanediol; Pdg) excretion. Luteal Pdg will be compared in the pulsatile FSH cycle to the daily dose subcutaneous (SQ) cycle. Patients who conceive in the cycle of study will not have their conception cycle included in the analysis.

  4 months

Study Arms (2)

Conventional Subcutaneous FSH Dosing

ACTIVE COMPARATOR

A daily gonadotropin dose (typically 75-450 IU) will be assigned and adjusted, based on clinical criteria and, if known, past response to hormones. Recombinant human FSH (rhFSH) will be given as a daily subcutaneous injection, as is performed, by patients at home, in routine clinical practice.

Drug: Follicle Stimulating Hormone

Pulsatile IV FSH Dosing

EXPERIMENTAL

participants will receive the same daily rhFSH dose (based on clinical practice criteria); however, it will be delivered via a portable infusion pump with reservoir (Avocet Infusion Pump, Eitan Medical LTD) that will provide an IV bolus (100-500 µl) every 90 minutes, a frequency that has previously been shown to result in physiologic ovulatory cycles in GnRH deficient women (Martin). The total gonadotropin dose delivered over a 24 hour period will be typically 75-450 IU, assigned based on standard of care clinical criteria (max dose is 900IU per clinical care guidelines). Participants will be provided with a 100mL preloaded reservoir, calibrated to deliver the approved standard of care dosing, in 16 boluses (100-500µl) over 24 hours (q 90min), for 7-12 days. Each 100 ml reservoir has capacity for 200 doses if the volume is 500 µl, which is sufficient for the typical 7- 12-day protocol.

Drug: Follicle Stimulating Hormone

Interventions

Follicle Stimulating Hormone DRUG

Pulsatile FSH administration via a portable pump.

Also known as: FSH

Conventional Subcutaneous FSH Dosing; Pulsatile IV FSH Dosing

Eligibility Criteria

• Age: 19 Years - 37 Years
• Gender Eligibility Details: Females are only being recruited because this study looks at ovarian response
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI between 30 kg/m2 and 40 kg/m
• Weight stability, i.e. no continued weight loss of \>1lb per week for a minimum of 4 weeks prior to enrollment
• Normal thyroid stimulating hormone (TSH) and prolactin
• Anti-Mullerian Hormone (AMH) \> 1 ng/ml or \< 8 ng/mL
• Willingness to postpone conception for the first study cycle
• Involuntary inability to conceive for at least 6 months
• No clinical diagnosis of polycystic ovarian syndrome (PCOS)
• Documentation of ovulation with luteal progesterone \>6 ng/ml or positive ovulation predictor home testing
• Regular menstrual cycles 25-40 days in length
• Male partner (or sperm donor) with adequate sperm (\>14 million sperm per ml)
• Hysterosalpingogram or saline infusion sonography demonstrating at least one patent Fallopian tube and a normal uterine cavity
• Serum total and free testosterone within the 95% CIearance for women with obesity previously studied in our laboratory.
• Acceptance of the indwelling catheter and willingness to take part in the study

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Related Links

• Pulsatile gonadotropin administration in in-vitro fertilisation
• Estradiol Priming Improves Gonadotrope Sensitivity and Pro-Inflammatory Cytokines in Obes
• Acute recapitulation of the hyperinsulinemia and hyperlipidemia characteristic of metabolic syndrome suppresses gonadotropins.
• Closed intravenous administration of gonadotropin-releasing hormone: safety of extended peripheral intravenous catheterization
• Effects of pulsatile intravenous follicle- stimulating hormone treatment on ovarian function in women with obesity.
• Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are reduced in obese women.
• Gonadotropin response to insulin and lipid infusion reproduces the reprometabolic syndrome of obesity in eumenorrheic lean women: a randomized crossover trial.

MeSH Terms

Conditions

Infertility; Obesity

Interventions

Follicle Stimulating Hormone

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Nanette Santoro, MD

  University of Colorado School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Kuhn, MS

CONTACT

303-7245276; Katherine.Kuhn@cuanschutz.edu

Asma Giornazi, MS

CONTACT

303-724-5276; Asma.Gioranzi@ucdenver.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Examine effects of pulsatile FSH administration as a new method for stimulation in IVF

Study Record Dates

• First Submitted: May 10, 2024
• First Posted: May 16, 2024
• Study Start: October 1, 2024
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)