Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophosphamide as Determined by Questionnaires

Systemic Lupus Erythematosus (Sle) Clinical Trial

Official title:

Efficacy of Gonadotropin-releasing Hormone Agonist (GnRHa) in Ovarian Preservation in SLE Subjects Receiving Cyclophosphamide as Determined by Questionnaires

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05567198
• Other study ID #: 10001011
• Secondary ID: 001011-AR
• Status: Recruiting
• Start date: March 3, 2023
• Est. completion date: May 31, 2025

Study information

• Verified date: May 15, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Sarfaraz A Hasni, M.D.
• Phone: (301) 451-1599
• Email: hasnisa[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background:

Systemic lupus erythematosus (SLE) is a disease that affects females nine times more often than males. People with SLE are often treated with cyclophosphamide (CYC). But CYC can damage a woman s ovaries; it may cause infertility. A drug called GnRHa is sometimes given to protect the ovaries during CYC therapy. But no one really knows how effective GnRHa treatment is. This natural history survey will compare women who received GnRHa during CYC therapy with those who did not.

Objective:

To find out whether GnRHa can help protect women s ovaries during CYC.

Eligibility:

Women under age 40 years starting CYC treatment with or without GnRHa.

Design:

This study will do 2 things: It will conduct patient surveys. It will collect data from medical records.

Participants will complete a one-time survey. They will answer questions about their menstrual cycle. They will be asked about their history of pregnancy or infertility.

Participants can take the survey in 4 ways:

On paper, sent through the mail.

Online, in a secure web page managed by the NIH.

By phone.

In person, during a routine visit to the NIH clinic.

The survey will take about 30 minutes.

Participants medical records will be reviewed. Researchers will look for data about the participants SLE disease. This may include their symptoms and the results of their blood tests. It may also include the details of prior treatments.

Researchers will also collect data about participants reproductive history. This may include their personal or family history of infertility. It may include any fertility treatments and any sexually transmitted infections.

Description:

Study Description: SLE patients with life-threatening lupus manifestations are often treated with cyclophosphamide (CYC), which has known cytotoxic effects on ovarian reserve. Co-administration of Gonadotropinreleasing hormone agonist (GnRHa) is suggested to protect ovaries from the cytotoxic effects of CYC but there is lack of data to support this. We hypothesize that the co-administration of a GnRH agonist for the duration of CYC therapy will exert protective effects on ovarian reserve and function in SLE females. We plan to do a patient survey and a retrospective data collection to compare ovarian function in subjects who received CYC with GnRHa to those who received CYC without GnRHa.

Objectives:

Primary Objective: Determine the effectiveness of GnRH-a in preventing primary ovarian insufficiency (POI) in female SLE patients getting cyclophosphamide treatment.

Secondary Objectives: Determine the effects of SLE disease activity, damage accrual, cumulative dose of cyclophosphamide and other demographic and clinical variables in preventing primary ovarian insufficiency.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

• ELIGIBILITY CRITERIA:

• INCLUSION CRITERIA: Group 1: SLE patients receiving CYC alone

SLE females <40 years at the beginning of CYC treatment without GnRH-a cotreatment.

-EXCLUSION CRITERIA: Group 1: SLE patients receiving CYC alone

Females >40 years at the beginning of CYC treatment; any females with a prior history of reproductive disorders, infertility, or untreated sexually transmitted infections (STIs).

-INCLUSION CRITERIA: Group 2: SLE patients receiving both CYC and leuprolide acetate (GnRH-a). Leuprolide acetate was injected at a dose of either 3.75 mg/month or 11.25mg/every 3 months.

SLE females <40 years at the beginning of CYC treatment with GnRH-a cotreatment.

-EXCLUSION CRITERIA: Group 2: SLE patients receiving both CYC and leuprolide acetate (GnRH-a). Leuprolide acetate was injected at a dose of either 3.75 mg/month or 11.25mg/every 3 months.

Females >40 years at the beginning of CYC treatment; any females with a prior history of reproductive disorders, infertility, or untreated STIs.

-Group: Control subjects.

Age-matched female SLE patients without a history of reproductive disorders, infertility, or untreated STIs, who have not received CYC either with or without GnRH-a.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Menopause, Premature
• Primary Ovarian Insufficiency
• Systemic Lupus Erythematosus (Sle)

Locations

Country	Name	City	State
United States	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Friedman RC, Clarkin JF, Corn R, Aronoff MS, Hurt SW, Murphy MC. DSM-III and affective pathology in hospitalized adolescents. J Nerv Ment Dis. 1982 Sep;170(9):511-21. doi: 10.1097/00005053-198209000-00001. No abstract available. — View Citation

Kiriakidou M, Cotton D, Taichman D, Williams S. Systemic lupus erythematosus. Ann Intern Med. 2013 Oct 1;159(7):ITC4-1. doi: 10.7326/0003-4819-159-7-201310010-01004. No abstract available. — View Citation

Stamenovic B. [Effect of increased chloride on the spontaneous release of acetylcholine in the neuromuscular synapses of amphibia poisoned with Clostridium toxin Type A]. Vojnosanit Pregl. 1972 Mar;29(3):139-44. No abstract available. Serbian. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	POI	The primary outcome variable is POI, and we want to determine whether GnRH-a coadministration with CYC protects against POI incidence in pre-menopausal SLE females. The age of menopause onset will be collected from previous medical records or survey responses and compared across all three groups. Onset of menopause prior to the age of 40 will be considered POI, whereas menopause onset beyond the age of 40 will be considered natural menopause.	End of study
Secondary	Record Effects of CYC administration with GnRH-a on menstrual cycle	- Menses cycles will be classified as either regular (consistently having a period of normal duration each month) or irregular (frequent, infrequent, or absent periods). Classifications of irregular cycle subcategories will be provided, which include polymenorrhea (frequent periods with a cycle length <21 days), oligomenorrhea (infrequent menses with cycle length between 37 to 90 days), or amenorrhea (absence of a period for >90 days). - Menopausal signs and symptoms will include vaginal dryness, hot flashes, chills, sleeping disturbances, night sweats, mood changes, weight gain, loss of breast fullness, thinning hair, or dry skin. - Inability to conceive will be defined as 12 months of trying to conceive without success.	End of study
Secondary	SLE disease activity as measured by SELENA-SLEDAI score at the start of CYC treatment	These include SLE disease activity as measured by SELENA-SLEDAI score at the start of CYC treatment, damage index score as measured by SLICC/ACR DI, cumulative CYC dose, and age at the time of beginning CYC.	End of study