Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene Mutations in Acromegaly

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by TC Erciyes University
Sponsor:
Information provided by (Responsible Party):
ZULEYHA KARACA, TC Erciyes University
ClinicalTrials.gov Identifier:
NCT01902420
First received: July 12, 2013
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

Acromegaly is a rare disease caused by growth hormone (GH) secreting pituitary adenoma in more than 95% of cases. Acromegaly can be seen sporadically or may be associated with a variety of genetic syndromes such as Multiple Endocrine Neoplasia Type 1, Carney Complex, familial isolated pituitary adenoma (FIPA) and Mc-Cune Albright Syndrome. The accompanying features of these syndromes and family history are helpful in the differential diagnosis. Aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene mutations can be seen sporadically as well as in FIPA. But the prescience of the presence of AIP mutation is limited by positive family history and early-onset of acromegaly. Furthermore, the probability of the patient to be the index case of the family should not be ignored.

Screening for AIP gene mutation is recommended in patients with pituitary adenomas of childhood-onset, GH or prolactin secreting tumors who are diagnosed before the age of 30 years and positive family history in two or more family members according to present evidence in the literature. It is also known that AIP mutation is usually associated with more aggressive clinical behavior due to unclarified reasons.

The prevalence of AIP mutation in Turkish population and types of mutations have not been defined previously. The primary aim of the present study is to define the AIP gene mutation prevalence and the relation with clinical and tumour behaviour in a subgroup of Turkish acromegalic patients. If AIP gene mutation is detected in some patients, it will be possible to screen the family of the patient for the presence of AIP mutation or at least for the presence of pituitary adenoma.

Acromegalic patients who are followed in Erciyes University Medical School Department of Endocrinology will be enrolled into the study. After DNA isolation, each exon of AIP gene including splicing points will be reproduced by polymerase chain reaction (PCR) and will be analyzed for the presence of mutation by sequence analysis. The cases will be analyzed further in means of clinical features according to presence of AIP gene mutation.

The prevalence of AIP gene mutation, clinical reflection of presence of AIP mutation will be determined and genetic consultation will be given to the carriers of AIP gene mutation at the end of the study.


Condition
Acromegaly

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Investigation of Prevalence and Clinical Effects of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene Mutations With DNA Sequence Analysis in Acromegaly Patients in Turkey

Resource links provided by NLM:


Further study details as provided by TC Erciyes University:

Primary Outcome Measures:
  • number of acromegalic patients with AIP mutation [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • number of acromegalic patients with aggressive tumor with AIP mutation [ Time Frame: up to 18 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

DNA samples


Estimated Enrollment: 80
Study Start Date: November 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
patients with acromegaly
patients with acromegaly caused by a growth hormone secreting pituitary adenoma
healthy control
healthy volunteers without a personal or family history of pituitary adenoma

Detailed Description:

Screening for AIP gene mutation is recommended in patients with pituitary adenomas of childhood-onset, GH or PRL secreting tumors who are diagnosed before the age of 30 years and positive family history in two or more family members according to present evidence in the literature. It is also known that AIP mutation is usually associated with more aggressive clinical behavior due to unclarified reasons.

The prevalence of AIP mutation in Turkish population and types of mutations have not been defined previously. The primary aim of the present study is to define the AIP gene mutation prevalence and the relation with clinical and tumour behavior in a subgroup of Turkish acromegalic patients. If AIP gene mutation is detected in some patients, it will be possible to screen the family of the patient for the presence of AIP mutation or at least for the presence of pituitary adenoma.

Acromegalic patients who are followed in Erciyes University Medical School Department of Endocrinology will be enrolled into the study. The clinical and laboratory data will be recorded and the remission status of the patients will be determined. Each exon of AIP gene including splicing points will be reproduced by PCR and will be analyzed for the presence of mutation by sequence analysis. Genomic DNA will be isolated from peripheral blood samples of acromegalic patients by using the QIAamp DNA blood mini kit (QIA-GEN, Milano, Italy) according to the manufacturer's instruction. Fifty nanograms of genomic DNA will be amplified with primers as reported. The entire AIP gene will be examined acromegaly patients and healthy control group. Each AIP exon from each DNA sample will be amplified using PCR. Six AIP exons will be amplified using the Thermo Taq DNA polymerase and following conditions: an initial denaturation at 96°C for 5 min, followed by 34 cycles of 94°C for 45 s, 60°C for 45 s, 72°C for 1 min, then a final extension step at 72°C for 7 min.PCR amplifications will be checked on a 2 % agarose gel. PCR products will be purified by PCR purification kit. Sequential alterations will be determined by bidirectional sequencing. Six AIP exons will be sequenced by using Beckman CEQ 8000.

The cases will be analyzed further in means of clinical features according to presence of AIP gene mutation.

The prevalence of AIP gene mutation, clinical reflection of presence of AIP mutation will be determined and genetic consultation will be given to the carriers of AIP gene mutation at the end of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

acromegaly patients

Criteria

Inclusion Criteria:

* Patients with acromegaly

Exclusion Criteria:

* Patients with acromegaly due to ectopic GH or GHRH secreting tumors

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01902420

Locations
Turkey
Erciyes University Medical School Department of Endocrinology Recruiting
Kayseri, Turkey, 38030
Contact: Fahrettin Kelestimur, Prof    00903524374922    fktimur@erciyes.edu.tr   
Principal Investigator: Zuleyha Karaca, Assoc Prof         
Principal Investigator: Serpil Taheri, Assis Prof         
Sub-Investigator: Fatih Tanriverdi, Assoc Prof         
Sub-Investigator: Kursad Unluhizarci, Prof         
Principal Investigator: Fahrettin Kelestimur, Prof         
Sponsors and Collaborators
TC Erciyes University
Investigators
Principal Investigator: Zuleyha Karaca Erciyes University Medical School Department of Endocrinology Kayseri/Turkey
Principal Investigator: Serpil Taheri Erciyes University Medical School Department of Medical Biology, Kayseri/Turkey
Study Director: Fahrettin Kelestimur Erciyes University Medical School Department of Endocrinology Kayseri/Turkey
Study Chair: Fatih Tanriverdi Erciyes University Medical School Department of Endocrinology Kayseri/Turkey
Study Chair: Kursad Unluhizarci Erciyes University Medical School Department of Endocrinology Kayseri/Turkey
  More Information

No publications provided

Responsible Party: ZULEYHA KARACA, Assoc. Prof Dr Zuleyha KARACA, TC Erciyes University
ClinicalTrials.gov Identifier: NCT01902420     History of Changes
Other Study ID Numbers: 113S432
Study First Received: July 12, 2013
Last Updated: July 18, 2013
Health Authority: Turkey: Ethics Committee

Additional relevant MeSH terms:
Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 22, 2014