AdenomyosisNAPPED IINCT02197923
Norwegian Adenomyosis Study II: Gene Expression Profiling of Adenomyosis
An observational study of Adenomyosis, run by Oslo University Hospital at 1 site in Norway.
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. Read more about this study
- Who is it for?
- Ages 30 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Adenomyosis
- What is being tested?
- Myometrial biopsy and endometrial biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 80 participants
- Where
- 1 siteNorway
- Study dates
- 6 Aug 2014to 1 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: women referred to our clinic and volunteering to participate
Who may be able to join
- Premenopausal women aged 30 - 50 years old scheduled for vaginal, abdominal or laparoscopic total hysterectomy one or more of the following clinical symptoms:
- bleeding disorders (menorrhagia, irregular bleeding, hypermenorrhoea),
- chronic pelvic pain,
- dysmenorrhoea,
- or dyspareunia junction zone definable
Who cannot join
- postmenopausal women,
- pregnancy
- gynecological cancer
- GnRH analog therapy or systemic hormone therapy in the last three months prior to hysterectomy
- junctional zone not identifiable
Trial locations and contacts
1 site in 1 country.
Norway1 site
Gynecological department, Oslo University Hospital, Ullevål
Oslo, 0382
About this study
Official title: Norwegian Adenomyosis Study: Pathophysiology, Peristalsis, Expression Profiling and Diagnosis, Part 2
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.
Read more
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.
Read the detailed 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.
- Conditions
- Adenomyosis
- Being tested
- Myometrial biopsy, endometrial biopsy
- Keywords
- Menorrhagia, Dysmenorrhea, Pelvic pain, expression profiling, uterine biopsies, serum hormones
- Medical subject headings
- Adenomyosis, Menorrhagia, Dysmenorrhea, Pelvic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Myometrial biopsyProcedure or surgery
transvaginal ultrasound guided biopsy of the myometria
endometrial biopsyProcedure or surgery
Also called Pipelle
transcervical endometrial biopsy
| Study group | Role | What they receive |
|---|---|---|
| Biopsy: adenomyosis | Myometrial biopsy Pipelle Receives: Procedure: Myometrial biopsy; Procedure: endometrial biopsy | |
| Biopsy: Healthy | Myometrial Biopsy Pipelle Receives: Procedure: Myometrial biopsy; Procedure: endometrial biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity and specificity of biopsies for adenomyotic tissue in percent (%)
Sensitivity and specificity of ultrasound guided myometrial biopsies for adenomyotic tissue
Measured: At time of hysterectomy
Secondary outcomes (8)
multiple comparison of gene expression, measured in fold
Expression profile for proliferative and invasive genes in adenomyotic tissue and surrounding stromal cells compared to healthy individuals, in fold
Measured: at time of biopsy taking
Frequency of complications related to biopsy taking in percent (%)
Measured: through 1 hour after biopsytaking
Serum levels of prolactin in mU/L
Serum levels of prolactin
Measured: at time of hysterectomy
Serum level of ER, in nmol/L
Serum level of estrogen.
Measured: at time of hysterectomy
Serum levels of FSH in U/L
Levels of follicle stimulating hormone.
Measured: at time of hysterectomy
Serum levels of AMH in pmol/L
Levels of Anti-Mullerian hormone.
Measured: at time of hysterectomy
Serum levels of LH in U/L
Levels of luteinizing hormone.
Measured: at time of hysterectomy
difference hormone serum-levels in fold
Comparison of serum-levels of PRL, FSH, AMH, LH and ER in patients with and without adenomyosis
Measured: at time of hysterectomy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2014 (estimated)
- Study start6 Aug 2014
- Primary completion1 Nov 2023 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AdenomyosisStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oslo, Helse Sor-Ost
- Responsible party
- Principal investigator, Tina Tellum, Oslo University Hospital
- Investigators
- Erik Qvigstad, PhD, MD, Study chair, Oslo University Hospital, UllevålTina Tellum, MD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02197923
- Sponsor's protocol ID
- 2014/637b
- Acronym
- NAPPED II
- Status last verified
- Mar 2023
- First submitted
- 17 Jul 2014
- Last updated
- 23 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Norwegian Adenomyosis Study: Pathophysiology, Peristalsis, Expression Profiling and Diagnosis, Part 2
- ClinicalTrials.gov ID
- NCT02197923
- Acronym / sponsor ID
- NAPPED II / 2014/637b
- Conditions
- Adenomyosis
- Keywords
- Menorrhagia, Dysmenorrhea, Pelvic pain, expression profiling, uterine biopsies, serum hormones
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- University of Oslo, Helse Sor-Ost
- Study start
- 6 Aug 2014 (actual)
- Primary completion
- 1 Nov 2023 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 23 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Biopsy: adenomyosis | – | Procedure: Myometrial biopsy, Procedure: endometrial biopsyMyometrial biopsy Pipelle |
| Biopsy: Healthy | – | Procedure: Myometrial biopsy, Procedure: endometrial biopsyMyometrial Biopsy Pipelle |
Who may qualify
- Ages
- 30 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- women referred to our clinic and volunteering to participate
Key inclusion criteria (5 listed)
- Premenopausal women aged 30 - 50 years old scheduled for vaginal, abdominal or laparoscopic total hysterectomy one or more of the following clinical symptoms:
- bleeding disorders (menorrhagia, irregular bleeding, hypermenorrhoea),
- chronic pelvic pain,
- dysmenorrhoea,
- or dyspareunia junction zone definable
Key exclusion criteria (5 listed)
- postmenopausal women,
- pregnancy
- gynecological cancer
- GnRH analog therapy or systemic hormone therapy in the last three months prior to hysterectomy
- junctional zone not identifiable
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Myometrial biopsytransvaginal ultrasound guided biopsy of the myometria | Procedure or surgery | Biopsy: Healthy, Biopsy: adenomyosis |
| endometrial biopsyAlso: Pipelletranscervical endometrial biopsy | Procedure or surgery | Biopsy: Healthy, Biopsy: adenomyosis |
Primary outcome
Sensitivity and specificity of biopsies for adenomyotic tissue in percent (%)
Time frame: At time of hysterectomy
Sensitivity and specificity of ultrasound guided myometrial biopsies for adenomyotic tissue
8 secondary outcomes
multiple comparison of gene expression, measured in fold
Time frame: at time of biopsy taking
Frequency of complications related to biopsy taking in percent (%)
Time frame: through 1 hour after biopsytaking
Serum levels of prolactin in mU/L
Time frame: at time of hysterectomy
Serum level of ER, in nmol/L
Time frame: at time of hysterectomy
Serum levels of FSH in U/L
Time frame: at time of hysterectomy
Serum levels of AMH in pmol/L
Time frame: at time of hysterectomy
Serum levels of LH in U/L
Time frame: at time of hysterectomy
difference hormone serum-levels in fold
Time frame: at time of hysterectomy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erik Qvigstad, PhD, MD study chair
Oslo University Hospital, Ullevål
Tina Tellum, MD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adenomyosis, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity and specificity of biopsies for adenomyotic tissue in percent (%) (time frame: At time of hysterectomy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2023.