GARM II: A Study on the Genetics of Age-related Maculopathy

Age-related Macular Degeneration Clinical Trial

Official title:

Genetics of Age Related Maculopathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01115387
• Other study ID #: 08-11-008
• Secondary ID: 5R01EY009859
• Status: Active, not recruiting
• Start date: October 6, 2011
• Est. completion date: March 2027

Study information

• Verified date: November 2023
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The original study (GARM I) has been conducted for more than 18 years at the University of Pittsburgh Medical Center (UPMC). GARM II is a nationwide research study about age-related macular degeneration in the next generation of adults (49 to 65 years old). The purpose of this study is to identify the hereditary and exposure risk factors that lead to the development of ARM (Age related maculopathy).

Participants will communicate with the research staff through a protected and confidential website and use this website to complete a number of questionnaires during the course of the study (see below). For genetic analyses, the participants will mail in easily self-collected saliva samples in special containers. Eye photographs and eye health records are sent to the research center from local sources through the Internet. Individuals are not expected to come to UCLA in order to participate.

https://jseiclinres.jsei.ucla.edu/garm/

Participants will be expected to answer questionnaires or surveys about medical history, ocular history and visual symptoms, family history, smoking, dietary supplements and light exposure.

Description:

Age-related macular degeneration (ARM) is a major cause of vision loss in the elderly. It is thought that smoking and diet may contribute to the risk of developing the condition but it is clear that heredity plays a major role. Variations in two genes, CFH and HTRA1/ARMS2, have been found to strongly contribute to the risk of developing ARM, but there are additional genes that influence a person's chances of having this condition and how they will progress to vision loss. We are investigating these genetic variations that contribute to ARM so that we can eventually understand the causes of this complex condition. We study the genetic variations (SNPs) that are shared among ARM-affected individuals within families as well as compare the frequencies of genetic variations in ARM-affected individuals with those in unaffected persons who are matched in age, gender, and exposures. We are conducting studies with the DNA from our previous cohort of research participants as well as developing a prospective study of high-risk family members and their spouses to evaluate genetic risks and presymptomatic retinal changes. Our long-term goals are to develop new preventive therapies that can slow or halt the development of this disease and to be able to provide these treatments to those who are at greatest risk before they experience vision-threatening changes.

The goal of this study (GARM II) is to determine how the combination of genetic, dietary, health and exposure factors such as light, diet, and smoking contributes to one's risk of developing this condition. This is not a treatment study and does not involve any preventive therapies or direct treatments of ARM. We aim to find some insights for future preventive strategies through a group of people who are at a higher than normal risk for developing ARM (because of their family history) and their partners who represent the risk in the general population. Because ARM is a complex disease and is affected by many factors, we also want to know how other medical conditions may be associated or not with this eye condition.

Participants will communicate with the research staff through a protected, HIPAA-compliant and confidential website and use this website to complete a number of questionnaires during the course of the study. For genetic analyses, the participants will mail in easily self-collected saliva samples in special containers. Eye photographs and eye health records are sent to the research center from local sources through the Internet. Individuals are not expected to come to UCLA in order to participate.

https://jseiclinres.jsei.ucla.edu/garm/

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 603
• Est. completion date: March 2027
• Est. primary completion date: February 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 49 Years and older

Eligibility

Inclusion Criteria:

• Individuals should have an email account and access to the Internet in order to use the website for this study. Individuals who are unfamiliar or physically challenged with using computers may have another person assist them with reviewing messages, questions and entering information and making inquiries.

• ARM at-risk individuals between the ages of 49 to 65 years old who have at least one parent either deceased or alive with diagnosis of macular degeneration. This group includes the "third generation children" of our original GARM study.

• Individuals between the ages of 49 to 65 years old who are either a spouse or partner of an ARM at-risk adult (those individuals described above with a parent diagnosed with ARM).

• Individuals who have vision loss from ARM and a known family history of ARM (at least a brother, sister, or a parent). These individuals should have at least one at-risk child between the ages of 49 to 65 years old who is willing to participate in this study.

Exclusion Criteria:

• Inability to give informed consent. Adaptations will be provided to allow those who are unable to read because of vision loss to participate in the informed consent process.(Proxy)

• For the at risk individuals and their spouses/partners, they will be excluded if they do not have access and the ability to use a computer that is connected to the Internet.

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Age-related Maculopathy
• Macular Degeneration

Intervention

Other:
• Observational-1
Multiple questionnaires detailing family history, medical history, visual symptoms, smoking, environmental and dietary exposures. Prospective photography of the retina to detect early ARM-related changes A saliva or blood sample for genetic testing.
• Observational-2
A limited number of questionnaires and prior clinical documentation from eye care professionals of eye status with respect to ARM. No prospective retina photographs but ongoing follow-up for reported changes in ARM status. A saliva or blood sample for genetic testing.

Locations

Country	Name	City	State
United States	Jules Stein Eye Institute, Dept. of Ophthalmology David Geffen School of Medicine at UCLA	Los Angeles	California
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of California, Los Angeles	Jules Stein Eye Institute, National Eye Institute (NEI), University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (12)

Conley YP, Gorin MB. The genetics of age-related macular degeneration. Medsurg Nurs. 2003 Aug;12(4):238-41, 259. — View Citation

Conley YP, Jakobsdottir J, Mah T, Weeks DE, Klein R, Kuller L, Ferrell RE, Gorin MB. CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses. Hum Mol Genet. 2006 Nov 1;15(21):3206-18. doi: 10.1093/hmg/ddl396. Epub 2006 Sep 25. — View Citation

Conley YP, Thalamuthu A, Jakobsdottir J, Weeks DE, Mah T, Ferrell RE, Gorin MB. Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy. Hum Mol Genet. 2005 Jul 15;14(14):1991-2002. doi: 10.1093/hmg/ddi204. Epub 2005 Jun 1. — View Citation

Gorin MB. A clinician's view of the molecular genetics of age-related maculopathy. Arch Ophthalmol. 2007 Jan;125(1):21-9. doi: 10.1001/archopht.125.1.21. — View Citation

Gorin MB. A new vision for age-related macular degeneration. Eur J Hum Genet. 2005 Jul;13(7):793-4. doi: 10.1038/sj.ejhg.5201431. No abstract available. — View Citation

Gorin MB. The coming of age for age-related macular degeneration genetics. Ophthalmic Genet. 2005 Jun;26(2):57-9. doi: 10.1080/13816810590969914. No abstract available. — View Citation

Jakobsdottir J, Conley YP, Weeks DE, Ferrell RE, Gorin MB. C2 and CFB genes in age-related maculopathy and joint action with CFH and LOC387715 genes. PLoS One. 2008 May 21;3(5):e2199. doi: 10.1371/journal.pone.0002199. — View Citation

Jakobsdottir J, Conley YP, Weeks DE, Mah TS, Ferrell RE, Gorin MB. Susceptibility genes for age-related maculopathy on chromosome 10q26. Am J Hum Genet. 2005 Sep;77(3):389-407. doi: 10.1086/444437. Epub 2005 Jul 26. — View Citation

Jakobsdottir J, Gorin MB, Conley YP, Ferrell RE, Weeks DE. Interpretation of genetic association studies: markers with replicated highly significant odds ratios may be poor classifiers. PLoS Genet. 2009 Feb;5(2):e1000337. doi: 10.1371/journal.pgen.1000337. Epub 2009 Feb 6. — View Citation

Tikellis G, Sun C, Gorin MB, Klein R, Klein BE, Larsen EK, Siscovick DS, Hubbard LD, Wong TY. Apolipoprotein e gene and age-related maculopathy in older individuals: the cardiovascular health study. Arch Ophthalmol. 2007 Jan;125(1):68-73. doi: 10.1001/archopht.125.1.68. — View Citation

Weeks DE, Conley YP, Tsai HJ, Mah TS, Rosenfeld PJ, Paul TO, Eller AW, Morse LS, Dailey JP, Ferrell RE, Gorin MB. Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions. Am J Ophthalmol. 2001 Nov;132(5):682-92. doi: 10.1016/s0002-9394(01)01214-4. — View Citation

Weeks DE, Conley YP, Tsai HJ, Mah TS, Schmidt S, Postel EA, Agarwal A, Haines JL, Pericak-Vance MA, Rosenfeld PJ, Paul TO, Eller AW, Morse LS, Dailey JP, Ferrell RE, Gorin MB. Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions. Am J Hum Genet. 2004 Aug;75(2):174-89. doi: 10.1086/422476. Epub 2004 May 27. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence and prevalence of retinal findings associated with early (and more advanced) age-related maculopathy in the study cohorts.	The primary outcome measure is the presence or absence of early retinal changes with age-related maculopathy in order to develop and test a model which combines genetic, environmental and dietary risk factors to predict which at risk individuals are most likely to develop signs of age-related maculopathy within the study period.	5 years