Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02197923 |
| Other study ID # |
2014/637b |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 6, 2014 |
| Est. completion date |
December 1, 2024 |
Study information
| Verified date |
March 2023 |
| Source |
Oslo University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Adenomyosis is characterized by the appearance of endometrial cells in the muscular layer of
the uterus. It affects about 15-20% of the female population.
The symptoms of adenomyosis are heavy menstrual bleedings and painful menstruation
(dysmenorrhea) and in addition chronic pelvic pain. Subfertility and infertility have been
correlated with adenomyosis.
Parity, age and uterine abrasion increase the risk of adenomyosis. Hormonal factors such as
local hyperestrogenism and elevated levels of prolactin (PRL) have been identified, but
autoimmune and mechanical factors are also hypothesized.
Regarding treatment, the most effective measure is hysterectomy. As this is a very drastic
measure in younger women, levonogestrel-releasing intrauterine devices, Gonadotropin
releasing hormone (GnRH)-analogues, Danazol, uterine embolization and endometrial ablation
have been tried, but studies are few in number, retrospective, and have small sample sizes.
Adenomyosis has so far not been subject to extensive research efforts. The pathogenesis of
adenomyosis remains still unclear, there are not many satisfying treatment options and
diagnostics include mostly magnetic resonance imaging (MRI) and histology.
The investigators designed a series of 3 studies with a broad approach in understanding
adenomyosis. This is part 2.
In this study the investigators take both tissue samples and blood samples that will be
investigated in order to understand the basic processes leading to adenomyosis.
Description:
Biopsy of focal adenomyosis of the myometrium:
This will be an extension of the NAPPED1-study. The investigators will perform
ultrasound-guided transvaginal biopsies of the myometrium and collect venous blood samples.
As recent studies have suggested abnormalities in the regulation of specific genes in the
development of adenomyosis, the investigators want to investigate differentially expressed
genes in adenomyosis compared to eutopic endometrium. Using microarrays, the investigators
can simultaneously screen differences in expression of thousands of genes in samples from the
two groups. Profiling studies performed on endometrium of healthy individuals and of
endometriosis show results that enable identification of biological processes and molecular
mechanisms. Expression profiles can be used to identify molecular targets for therapeutic
purposes. There are some very interesting studies that investigate drug treatment on a
molecular level e.g. the effect of Danazol treatment on eutopic and ectopic endometrial
tissue, but intramural adenomyosis has not been subject to gene profiling yet.
Tissue samples can be easily obtained after hysterectomy, but those samples will only
represent older women, and cannot be used for consecutive monitoring of biochemical effects
of treatment, as the uterus is removed. In order to investigate the pathophysiology of
adenomyosis in younger women, and compare it to those in older individuals, as well as to
evaluate effects of treatment, it is necessary to be able to obtain in-vivo samples.
The plan is therefore to take transvaginal, ultrasound-guided biopsy-samples from the uterus
(myometrium) of all included patients at the beginning of their surgery, when the patient is
under full anesthesia. The safety of comparable procedures has been shown in prior studies,
but the investigators will further validate the safety of this method. The investigators
believe that an in-vivo biopsy is a safe measure, and that representative samples of
adenomyosis can be obtained.
The challenge with adenomyosis is that it is located intramyometrially. A transcervical
biopsy will contaminate the sample with eutopic endometria, therefore it is most meaningful
to take the biopsy transvaginally, but not through the cavity. After obtaining the biopsy
sample, it will be examined histologically by imprint, to confirm if glandular cells are
contained where expected. When good routines show a reliable level of specificity, the
investigators will go further by selecting approximately 10 patients for gene profiling of
adenomyosis. The investigators will also use endometrial biopsies (Pipelle) from those
patients to see if there is a difference between intramural adenomyosis and their eutopic
endometria. Most patients that undergo hysterectomy have taken a pipelle-biopsy routinely.
The levels of prolactin, Anti-müllerian hormone (AMH), Follicle stimulating hormone (FSH),
luteinizing hormone (LH) and estrogen will also be taken, in order to determine if the
severity of adenomyosis is only related to age as shown before, or also to hormonal activity.
