Natural History of Spinocerebellar Ataxia Type 7 (SCA7)

Brief Title

Natural History of Spinocerebellar Ataxia Type 7 (SCA7)

Official Title

Natural History of Spinocerebellar Ataxia Type 7 (SCA7)

Brief Summary


      Spinocerebellar ataxia type 7 (SCA7) is disease in which people have problems with
      coordination, balance, speech and vision. It is caused by a change in the ATXN7 gene. A
      mutation in this ATXN7 gene causes changes in eye cells, which can lead to vision loss. There
      is no cure for SCA7 but researchers are looking for possible treatments. Researchers need
      more information about SCA7. They want to collect vision and neurology related data from
      people with SCA7. They want to learn how and what changes in the eye and brain when the ATXN7
      gene isn t working properly.


      To learn more about SCA7 and its progression.


      People ages 12 and older with SCA7.


      Participants will be screened with medical history and genetic testing from a previous
      National Eye Institute study or their personal physician.

      Participants will have at least 7 visits over 5 years. They will have 2 visits during the
      first week of the study. Then they will be asked to come back every year for the next 5
      years. Each visit will last several days and will include:

        -  Medical and eye history

        -  Several eye tests: some will include dilating the pupil with eye drops and taking photos
           or scans of the eyes.

        -  Electroretinography (ERG): Participants will sit in the dark with their eyes patched for
           30 minutes. After this, the patches will be removed and contact lenses put into the
           eyes. They will watch flashing lights and information will be recorded.

        -  Neurological exams: Sensation, strength, coordination, reflexes, attention, memory,
           language, and other cognitive functions will be tested.

        -  Brain MRI: They will lie in a machine that takes pictures of the brain.

        -  Blood and urine tests

        -  Optional skin biopsy: About 3 millimeters of skin will be removed for more research
           testing; this is half the size of a pencil eraser.

Detailed Description


      Spinocerebellar Ataxia, type 7 (SCA7) is an autosomal dominant neurodegenerative disease
      characterized by progressive ataxia, retinal degeneration, and marked genetic anticipation.
      The objectives of this study are to 1) establish a cohort of participants with
      molecularly-confirmed SCA7 in anticipation of future clinical trials, 2) create a repository
      of plasma, DNA, and skin fibroblast samples from the accrued cohort of SCA7 participants, 3)
      formulate clinical outcome measures for future studies, and 4) acquire and perform
      preliminary analyses of data that may advance our understanding of the progression of retinal
      and neurodegeneration associated with molecularly-confirmed SCA7.

      Study Population:

      Twenty-five (25) participants, ages 12 and above, with molecularly-confirmed SCA7 will be
      accrued for this study.


      In this natural history study, participants will be followed for at least five years. Because
      three years may be required to enroll 25 participants, this study will last up to eight
      years. All participants will undergo a standardized medical/ophthalmic history and a complete
      baseline eye examination, including non-invasive electrophysiology (e.g.,
      electroretinography), psychophysiology (e.g., microperimetry, static perimetry), and
      diagnostic imaging examinations (e.g., optical coherence tomography). In addition,
      participants will undergo a detailed neurology exam, neuroimaging (MRI, including special
      sequences) and consult with speech pathology and/or other rehabilitation services, audiology,
      and neuropsychology.

      To establish baseline, the participants will undergo two separate detailed eye examinations
      and a single neurology/neuroimaging examination within a one to two week period. Afterwards,
      they will return to the NEI clinic annually until the last-enrolled participant reaches five
      years of follow-up. Therefore, this study will require a minimum of five study visits.
      Follow-up visits will consist of a single detailed eye exam, a single detailed
      neurology/neuroimaging exam, and follow-up with appropriate consultants. Participants may be
      seen at more frequent intervals at the investigators discretion, depending on the clinical
      and research situation. Participants will be required to submit a blood sample for research,
      and they will have the option to provide a skin biopsy to facilitate research at a cellular

      Outcome Measures:

      The primary outcome for this study is determination of the amplitude and time of photopic and
      scotopic responses on electroretinogram. Secondary outcomes include changes in visual acuity,
      microperimetry, peripheral visual field, color vision, macular thickness, and neurologic
      outcome variables. Exploratory outcomes for this study include: 1) the formulation of
      clinical outcome measures for future studies and 2) the acquisition and preliminary analysis
      of data that may advance our understanding of the progression of retinal and
      neurodegeneration associated with molecularly-confirmed SCA7. Cells from skin biopsies may be
      grown in the laboratory to better understand SCA7, including the evaluation of potential

Study Type


Primary Outcome

Amplitude and time of photopic and scotopic responses on electroretinogram

Secondary Outcome

 changes in visual acuity, microperimetry, color vision, macular thickness, neurologic (including neuroimaging) outcome variables, eye movement recordings (e.g., saccadic velocity) and results of neuropsychologic testing


Spinocerebellar Ataxia

Study Arms / Comparison Groups

 Affected Participants
Description:  Twenty-five (25) participants with molecularly confirmedSCA7


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

July 11, 2016

Completion Date

January 1, 2026

Primary Completion Date

January 1, 2026

Eligibility Criteria


        To be eligible, the following inclusion criteria must be met, where applicable.

          1. Participant must be 12 years of age or older.

          2. Participant must be able to understand and sign the protocol s informed consent
             document on their own behalf OR, in the case of a minor, have a legal guardian/parent
             with the ability to do the same.

          3. Participant must be able to produce a recordable electroretinogram (ERG).

          4. Participant must have the ability to cooperate the required testing. Participants
             unable to cooperate with one or more tests may be included only at the discretion of
             the Principal Investigator.

          5. Participant must be willing and able to provide a blood sample.

          6. Any female participant of childbearing potential must agree to have pregnancy testing
             prior to undergoing MRI.

          7. Participant has molecularly-confirmed, symptomatic SCA7, as defined by CAG repeat
             expansion in the ATXN7 gene of greater than 35 repeats. Accrual will be biased towards
             those with lower numbers of abnormal repeats (above 35 repeats) as they are most
             likely to be able to cooperate with testing. Participants who have clinical findings
             consistent with SCA7 and a relative who has had molecular diagnosis, may be included
             in the study with subsequent confirmation of the number of repeats. Patients who have
             clinical findings consistent with SCA7 but no molecular diagnosis may be evaluated
             under an NEI screening, genetics bank, or evaluation and treatment protocol with
             subsequent molecular diagnosis performed within six months of their initial visit.


        A participant is not eligible if any of the following exclusion criteria are present.

          1. Participant is unable to cooperate with ophthalmic/neurologic testing, including
             inability to undergo brain MRI without sedation.

          2. Participant has comorbidity, unrelated to ocular pathology, compromising the ability
             to view/image the retina and/or record an ERG.




12 Years - N/A

Accepts Healthy Volunteers



Laryssa A Huryn, M.D., (301) 451-3437, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

National Eye Institute (NEI)

Study Sponsor

Laryssa A Huryn, M.D., Principal Investigator, National Eye Institute (NEI)

Verification Date

January 25, 2021