Testosterone Treatment in a Patient With 17β-hydroxysteroid Dehydrogenase Type 3 Deficiency: an N-of-1 Study

NCT ID: NCT04831099

Last Updated: 2021-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-01

Study Completion Date

2022-07-26

Brief Summary

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A 38-year old women with a 46,XY disorder of sex development (DSD) based on a 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-HSD3) was seen at the department of Internal Medicine-Endocrinology at the Erasmus MC, Rotterdam, the Netherlands.

The patient presented with fatigue, concentration problems and feelings of restlessness. In the past, the patient had undergone a gonadectomy at 9 months of age. In a follow-up visit at the outpatient clinic, the patient mentioned that friends with DSD had successfully been treated with testosterone and the patient requested testosterone treatment for her complaints.

In the literature, nothing is known about the usefulness of testosterone treatment for women with 17β-HSD3. For other forms of 46,XY DSD like complete androgen insensitivity syndrome (CAIS), limited data are available about testosterone treatment. Two studies have compared the effects of estrogen and testosterone replacement therapy on psychological wellbeing, quality of life (QoL) and sexual function in women with CAIS. The results were not conclusive, as one of them found a positive effect of testosterone replacement therapy on sexual function compared to estrogen, whereas the other study found no differences.

In order to evaluate the effect of testosterone treatment independent of a possible placebo effect, the usefulness of testosterone treatment in this individual patient with 17β-HSD3 will be investigated in an N-of-1 trial in order to improve the clinical care for this patient.

The primary objective is to determine the efficacy of testosterone treatment for fatigue on an individual level in a patient with 17β-HSD3 as assessed with the Checklist Individual Strength (CIS-20).

Detailed Description

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A 38-year old women with a 46,XY disorder of sex development (DSD) based on a 17β-hydroxysteroid dehydrogenase type 3 deficiency (17β-HSD3) was seen at the department of Internal Medicine-Endocrinology at the Erasmus MC, Rotterdam, the Netherlands.

17β-HSD3 is a rare disorder characterized by a (despite the presence of a Y chromosome) female habitus in almost all newborns, with congenital agenesis of the uterus and ovaries. During puberty, patients with 17β-HSD3 often develop secondary male characteristics, such as deepening of the voice, male pattern body hair, and clitoromegaly.

The patient presented with fatigue, concentration problems and feelings of restlessness. In the past, the patient had undergone a gonadectomy at 9 months of age. In a follow-up visit at the outpatient clinic, the patient mentioned that friends with DSD had successfully been treated with testosterone and the patient requested testosterone treatment for her complaints. The patient was aware of the fact that the positive effect noticed by the patients' friends could be (partly) explained by placebo effect.

In the literature, nothing is known about the usefulness of testosterone treatment for women with 17β-HSD3. For other forms of 46,XY DSD like complete androgen insensitivity syndrome (CAIS), limited data are available about testosterone treatment. Two studies have compared the effects of estrogen and testosterone replacement therapy on psychological wellbeing, quality of life (QoL) and sexual function in women with CAIS. The results were not conclusive, as one of them found a positive effect of testosterone replacement therapy on sexual function compared to estrogen, whereas the other study found no differences.

In order to evaluate the effect of testosterone treatment independent of a possible placebo effect, the usefulness of testosterone treatment in this individual patient with 17β-HSD3 will be investigated in an N-of-1 trial in order to improve the clinical care for this patient.

The primary objective is to determine the efficacy of testosterone treatment for fatigue on an individual level in a patient with 17β-HSD3 as assessed with the Checklist Individual Strength (CIS-20).

Secondary objectives are to determine the effect of testosterone treatment on the QoL (5-level EQ-5D), testosterone, dehydroepiandorosterone (DHEA), and estradiol levels, on bone density, and on specific personalized goals that are important to the patient and her environment (Goal Attainment Scaling). To monitor the safety of testosterone treatment, hematocrit levels will be measured and the occurrence of adverse events will be evaluated.

Conditions

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Disorder of Sex Development, 46,XY

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

N-of-1 study: cross-over study in 1 patient with 2 cycles that each consists of 2 periods (one period of placebo and one period of active treatment).
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The participant and investigator are blinded. The investigator is also the care provider and investigator.

Study Groups

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Testosterone

Testosterone gel (20 mg/day) for 8 weeks per period.

Group Type EXPERIMENTAL

Testosterone gel

Intervention Type DRUG

The route of administration is transdermal.

Placebo

Placebo gel (20 mg/day) for 8 weeks per period.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

The route of administration is transdermal

Interventions

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Testosterone gel

The route of administration is transdermal.

Intervention Type DRUG

Placebo

The route of administration is transdermal

Intervention Type DRUG

Other Intervention Names

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AndroGel

Eligibility Criteria

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Inclusion Criteria

\- N/A

Exclusion Criteria

\- N/A
Minimum Eligible Age

38 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Erasmus Medical Center

OTHER

Sponsor Role lead

Responsible Party

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dr. Laura C. G. de Graaff-Herder

Principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Laura de Graaff, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine - Endocrinology, Erasmus MC, Rotterdam, the Netherlands

Locations

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Erasmus MC

Rotterdam, South Holland, Netherlands

Site Status

Countries

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Netherlands

Central Contacts

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Laura de Graaff, MD, PhD

Role: CONTACT

+31618843010

Facility Contacts

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Laura de Graaff, MD, PhD

Role: primary

+31618843010

Other Identifiers

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N-of-1 DSD

Identifier Type: -

Identifier Source: org_study_id

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