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Uterine FibroidNCT03444987

The Role of Fibroblast Activation in Uterine Fibroid

An observational study of Uterine Fibroid, run by Assiut University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Uterine fibroids (UFs), also called uterine leiomyomas or myomas, are steroid hormone-responsive, benign tumors of the smooth muscle compartment (myometrium) of the uterus. They are the most common neoplasm affecting women in their reproductive age. It is estimated that up to 77% of women develop UF in their life. Read more about this study

Who is it for?
Ages Up to 50 years, women onlyHealthy volunteers can take part
Conditions the study is for
Uterine Fibroid
What is being tested?
Measurement of protein expression in tissues.
Type of treatment
Pill or oral medicine
How many people
35 participants
Where
1 siteEgypt
Study dates
1 Mar 2018to 1 Mar 2020
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 Up to 50 years
  • Women only
  • Healthy volunteers accepted
  • Child, Adult

Study population: This study will include 35 premenopausal women (age ˂ 50 year) with uterine fibroids who are diagnosed through clinical gynecological, ultrasound and other auxiliary examinations. All selected patients will exhibit a normal coagulation function.

Who may be able to join

  • Premenopausal women (age ˂ 50) with uterine fibroids who are diagnosed through clinical gynecological, ultrasound and other auxiliary examinations.
  • Patients who exhibit a normal coagulation function.

Who cannot join

  • i. Patients who have a previous history of myomectomy or with ovarian malignancy and borderline tumors ii. Patients who are subsequently diagnosed with uterine adenomyosis. iii. Pregnant women. iv. Patients who receive hormonal treatment within three months before surgery. v. Patients with history of coronary artery disease, hypertension, liver cirrhosis or hematologic disorders.

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • Assiut university -Faculty of medicine- Departement of Biochemistry

    Asyut, 71111

Other trials in Egypt

About this study

Official title: A Novel Insight Into the Role of Fibroblast Activation and Autophagy in Uterine Fibroid

Uterine fibroids (UFs), also called uterine leiomyomas or myomas, are steroid hormone-responsive, benign tumors of the smooth muscle compartment (myometrium) of the uterus. They are the most common neoplasm affecting women in their reproductive age. It is estimated that up to 77% of women develop UF in their life. UFs are one of the leading causes of hospitalisations for gynaecological disorders and are the most frequent reason for hysterectomy. According to relevant literature, 40%-60% of all the hysterectomies performed are due to the presence of UFs.

Read the detailed description
  • Uterine fibroids (UFs) are steroid hormone-responsive, benign tumors of the smooth muscle compartment (myometrium) of the uterus .They are the most common neoplasm affecting women in their reproductive age. UFs are mainly composed of fibroid cells and a significant ECM component which principally consists of fibroblasts. Previous studies on the pathogenesis of uterine UF have mainly focused on the differentiation and proliferation of fibroid cells. However, the histologic features of fibroid tissue suggest that fibroblasts may play an important role in the generation of UF.
  • Fibroblast activation protein (FAP), fibroblast-specific marker, is a 95 kDa cell surface glycoprotein. It is a type II transmembrane serine protease and a member of proline-specific proteases family. Recent studies showed that the high expression of FAP is closely related to the occurrence of UF .Luo et al 2015 were the first who suggested that estrogen could stimulate fibroblast activation. In addition, they revealed that proliferative activity of fibroblast and the expression of FAP were significantly increased after estrogen stimulation. They also found that estrogen could promote the release of cytokines (TGFβ and IGF-1) and ECM components (collagen I, fibronectin, and laminin) from fibroblasts. Furthermore they found that silencing of FAP expression significantly decreased promotion effects of estrogen on TAF suggesting that FAP plays an important role in estrogen-mediated fibroblast activation.
  • Autophag (eating of self) is a collection of processes that enables the cells to digest and recycle their cytoplasmic contents, such as toxic protein aggregates, disused organelles and invading microorganisms. Dysregulation in autophagy process have been recently described in many neoplasms. However the role of autophagy in the pathogenesis of UFs is still unclear and further understanding of its regulation and significance will be needed.
  • The PI3K/AKT/mTOR signalling pathway is considered the main pathway involved in the initiation and regulation of autophagy. Previous studies found that reduced FAP significantly decreased the expression of phosphorylated AKT suggesting that FAP is an upstream factor modulating the PI3K/AkT. This study will be the first to study the link between fibroblast activation and autophagy in pathogenesis of UF through PI3K/AKT signaling pathway. Although several types of drugs (mostly antiproliferative agents) are available for UF treatment, none of them were introduced specifically as antifibrotic agents. Targeting such novel signaling pathway may be considered useful for future non surgical treatment of UF affecting both proliferative and fibrotic changes.
Conditions
Uterine Fibroid
Being tested
Measurement of protein expression in tissues.
Keywords
Uterine fibroid, FAP, Autophagy
Medical subject headings
Leiomyoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Measurement of protein expression in tissues.Genetic

    The followings markers will be estimated in tissue

    1. FAP, a marker of fibroblast activation, using quantitative real time polymerase chain reaction qRTPCR (mRNA level) and ELISA (protein level).
    2. Markers of autophagy including LC3 and p62 using qRTPCR (mRNA level) and by immunohistochemical analysis.
    3. Phosphorylated protein kinase B (pAKT) level by ELISA (protein level).
    4. Markers of oxidative stress (Malondialdehyde as lipid peroxide) by a colorimetric method.
    5. Reduced glutathione, an antioxidant marker by a colorimetric method
Study groups in NCT03444987
Study groupRoleWhat they receive
patients groupinclude 35 pre-menopausal women (age ˂ 50 years) enrolled to undergo hysterectomy for symptomatic UF at the women health hospitals, Assiut University. * The protein expression of the followings markers will be estimated in tumor tissue samples: 1. Fibroblast activation protein (FAP) will be measured by quantitative real time polymerase chain reaction qRTPCR (mRNA level) and ELISA (protein level). 2. Autophagy markers level (LC3 and p62) will be measured by qRTPCR (mRNA level) and by immunohistochemical analysis. 3. Phosphorylated protein kinase B (pAKT ) by ELISA (protein level). analysis. 4. Markers of oxidative stress (Malondialdehyde as lipid peroxide) by a colorimetric method. 5. Reduced glutathione, an antioxidant marker by a colorimetric method .
Receives: Genetic: Measurement of protein expression in tissues.
Control groupinclude 35 normal myometrial tissue samples obtained 1 cm away from the fibroid capsule from the same patients. * The protein expression followings markers will be estimated in normal myometrial tissue samples 1. Fibroblast activation protein (FAP) will be measured by quantitative real time polymerase chain reaction qRTPCR (mRNA level) and ELISA (protein level). 2. Autophagy markers level (LC3 and p62) will be measured by qRTPCR (mRNA level) and by immunohistochemical analysis. 3. Phosphorylated protein kinase B (pAKT) by ELISA (protein level). 4. Markers of oxidative stress (Malondialdehyde as lipid peroxide) by a colorimetric method. 5. Reduced glutathione, an antioxidant marker by a colorimetric method .
Receives: Genetic: Measurement of protein expression in tissues.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Comparing FAP and autophagy markers in patient and control groups.

    Explore difference in level of fibroblast activation marker (FAP) and autophagy markers (LC3 and P62) in UF tissue samples compared to normal myometrial samples (1 cm from the UF lesion).

    Measured: 1 year

Secondary outcomes (1)
  1. Study signaling pathway linking FAP and autophagy which ma considered as a therapeutic target

    Investigate the correlation between fibroblast activation and autophagy through PI3/AKT signaling pathway and their role in the pathogenesis of UF through estimation of AKT protein expression in UF tissue samples compared to normal myometrial samples 1 cm from the UF lesion.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2018
  2. Study start1 Mar 2018
  3. Primary completion1 Nov 2019
  4. Study completion1 Mar 2020

Resources

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
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03444987
Sponsor's protocol ID
UF
Status last verified
Feb 2021
First submitted
20 Feb 2018
Last updated
9 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • McWilliams MM, Chennathukuzhi VM. Recent Advances in Uterine Fibroid Etiology. Semin Reprod Med. 2017 Mar;35(2):181-189. doi: 10.1055/s-0037-1599090. Epub 2017 Mar 9.

    PubMed 28278535
  • Moore AB, Yu L, Swartz CD, Zheng X, Wang L, Castro L, Kissling GE, Walmer DK, Robboy SJ, Dixon D. Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture. Cell Commun Signal. 2010 Jun 10;8:10. doi: 10.1186/1478-811X-8-10.

    PubMed 20537183
  • Rasanen K, Vaheri A. Activation of fibroblasts in cancer stroma. Exp Cell Res. 2010 Oct 15;316(17):2713-22. doi: 10.1016/j.yexcr.2010.04.032. Epub 2010 May 6.

    PubMed 20451516
  • Wang H, Wu Q, Liu Z, Luo X, Fan Y, Liu Y, Zhang Y, Hua S, Fu Q, Zhao M, Chen Y, Fang W, Lv X. Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis. 2014 Apr 10;5(4):e1155. doi: 10.1038/cddis.2014.122.

    PubMed 24722280
  • Islam MS, Ciavattini A, Petraglia F, Castellucci M, Ciarmela P. Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics. Hum Reprod Update. 2018 Jan 1;24(1):59-85. doi: 10.1093/humupd/dmx032.

    PubMed 29186429
  • Luo N, Guan Q, Zheng L, Qu X, Dai H, Cheng Z. Estrogen-mediated activation of fibroblasts and its effects on the fibroid cell proliferation. Transl Res. 2014 Mar;163(3):232-41. doi: 10.1016/j.trsl.2013.11.008. Epub 2013 Nov 20.

    PubMed 24316382
  • Bainbridge TW, Dunshee DR, Kljavin NM, Skelton NJ, Sonoda J, Ernst JA. Selective Homogeneous Assay for Circulating Endopeptidase Fibroblast Activation Protein (FAP). Sci Rep. 2017 Oct 2;7(1):12524. doi: 10.1038/s41598-017-12900-8.

    PubMed 28970566
  • Hamson EJ, Keane FM, Tholen S, Schilling O, Gorrell MD. Understanding fibroblast activation protein (FAP): substrates, activities, expression and targeting for cancer therapy. Proteomics Clin Appl. 2014 Jun;8(5-6):454-63. doi: 10.1002/prca.201300095. Epub 2014 Mar 24.

    PubMed 24470260

Questions about this trial

What is this clinical trial studying?

An observational study of Uterine Fibroid, run by Assiut University at 1 site in Egypt.

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 2 inclusion and 1 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: finished, as of the sponsor's last update on 9 Feb 2021. 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 Egypt. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Comparing FAP and autophagy markers in patient and control groups. (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03444987, which also lists 8 linked publications.

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 9 Feb 2021.

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