Clinical trial NCT04831099: Testosterone Treatment in a Patient With 17β-hydroxysteroid Dehydrogenase Type 3 Deficiency: an N-of-1 Study
Official title: Testosterone Treatment in a Patient With 17β-hydroxysteroid Dehydrogenase Type 3 Deficiency: an N-of-1 Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Disorder of Sex Development, 46,XY
Keywords: 17-beta-hydroxysteroid dehydrogenase type 3 deficiency
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2021-04-05
Enrollment: 1
Sex: FEMALE
Minimum age (years): 38
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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 purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

- N/A

Exclusion Criteria:

- N/A

The study is especially designed for a specific female patient. The patient is 38 years old at the moment. Since the study is especially designed for this patient, there are no formal inclusion and exclusion criteria.

Primary outcomes:
measure: Fatigue (Checklist of Individual Strength)
timeFrame: Baseline to 420 days
Secondary outcomes:
measure: Quality of Life (5-level EQ-5D)
timeFrame: Baseline to 420 days
measure: Laboratory levels
timeFrame: Baseline to 420 days
measure: Bone density
timeFrame: Baseline to 420 days
measure: Goal attainment scaling
timeFrame: Baseline to 420 days
measure: Number of adverse events
timeFrame: Baseline to 450 days
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-Holland
Study officials:
affiliation: Department of Internal Medicine - Endocrinology, Erasmus MC, Rotterdam, the Netherlands
name: Laura de Graaff, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: