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| ID | Type | Description | Link |
|---|---|---|---|
| FD006029-01 | Other Grant/Funding Number | FDA |
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| Name | Class |
|---|---|
| University of Florida | OTHER |
| University of California, Los Angeles | OTHER |
| Food and Drug Administration (FDA) | FED |
| Friedreich's Ataxia Research Alliance |
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The purpose of this study is to identify ways to follow progression of Friedreich's Ataxia (FA) and be able to measure changes over time in children with FA. Participants will have biannual visits to observe how the disease progresses over time and determine the rate of progression.
Funding Source- Food and Drug Administration Office of Orphan Products Development (FDA OOPD).
Investigators seek to identify biological and clinical tests to be used in future clinical trials. The purpose of this research study is to learn more about Friedreich's Ataxia (FA) progression in children. There will be biannual visits which will include a core set of tests and procedures. These include: a collection of medical history, detailed neurological exam, ataxia scales, and health questionnaires. At each visit, blood and cheek swab samples will be obtained to monitor frataxin levels.
A select number of Children's Hospital of Philadelphia (CHOP) participants will have the opportunity to participate in further procedures to better understand how FA affects different tissues. These include a Magnetic Resonance Imaging (MRI) scan and a Motor Evoked Potentials (MEP) procedure.
The MRI scan analyzes how muscle activity is affected in FA. The magnet will be used to capture images of the calf muscle before and after exercising on an ergonomic foot pedal.
The MEP procedure measures how strong the connection is between the brain's motor cortex and a selected body part, specifically the participant's dominant hand.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| FA Children | Children between the ages of 2 and 18 with genetically confirmed Friedreich's Ataxia |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score | The Friedreich Ataxia Rating Scale (FARS) measures neurological function in FA. It is a composite measure reflecting neural substrates with five-subscales (sections A to E), measuring bulbar function, upper limb coordination, lower limb coordination, peripheral nerves, and upright stability. The modified FARS (mFARS) shortens the bulbar subscale to 2 items and excludes the peripheral nerve subscale. Total scoring is a summation of subscales, with a maximum score of 93 points for mFARS and 125 for FARS. The mFARS score ranges for each subscale are: Bulbar: 0 - 5, Upper Limb: 0 - 36, Lower Limb: 0 - 16, Upright Stability: 0 - 36. The overall change in mFARS and its sub scores across 3 years was the outcome measure analyzed at 0, 1, 2, and 3 year visits. Each subsection has a minimum score of 0, indicating minimal effect for that component. Maximum values per section vary based on the tasks performed in each subsection; a higher score indicates greater dysfunction on that component. | Baseline up to 36 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Timed 25-Foot Walk (T25FW) Test | The timed 25-foot walk (T25FW) test examines gait speed. The participant walks the distance of 25 feet as fast and safe as possible. Participants may use assistive devices during this task. The T25FW test was analyzed at 0, 1, 2, and 3 year visits. | Baseline up to 36 Months |
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Inclusion Criteria:
Exclusion Criteria:
1) Inability to complete study evaluations
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This study will primarily take place at the Children's Hospital of Philadelphia (CHOP), with a select number of subjects only participating in the clinical testing at the University of Florida and University of California Los Angeles (UCLA). The investigators expect to recruit approximately 100 children across all three sites and study each of them over a 3 year period. Children with a genetically or clinically confirmed diagnosis of Friedreich's Ataxia (FA) will be offered participation.
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| Name | Affiliation | Role |
|---|---|---|
| David Lynch, MD, PhD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Los Angeles | Los Angeles | California | 90095 | United States | ||
| University of Florida |
Overall, among 108 individuals enrolled, 19 were excluded from the analysis population for one or more reasons. These included missing mFARS data at baseline or follow-up, early disease stage, and inability to ambulate at baseline.
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| ID | Title | Description |
|---|---|---|
| FG000 | FA Children | The present study enrolled 108 children aged 6.7 to 18y with genetically confirmed FRDA (Friedreich Ataxia) between Oct 2017 and October 2019. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Overall, among 108 individuals enrolled, 19 were excluded from the analysis population for one or more reasons.
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| ID | Title | Description |
|---|---|---|
| BG000 | FACHILD | The population enrolled in this study was a young, severely affected cohort, indicated by high GAA1 repeat lengths and early ages of onset. It was a mixed early/typical FRDA population, suggesting a certain level of diversity despite tight pediatric enrollment criteria. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in mFARS (Modified Friedreich's Ataxia Rating Scale) Score | The Friedreich Ataxia Rating Scale (FARS) measures neurological function in FA. It is a composite measure reflecting neural substrates with five-subscales (sections A to E), measuring bulbar function, upper limb coordination, lower limb coordination, peripheral nerves, and upright stability. The modified FARS (mFARS) shortens the bulbar subscale to 2 items and excludes the peripheral nerve subscale. Total scoring is a summation of subscales, with a maximum score of 93 points for mFARS and 125 for FARS. The mFARS score ranges for each subscale are: Bulbar: 0 - 5, Upper Limb: 0 - 36, Lower Limb: 0 - 16, Upright Stability: 0 - 36. The overall change in mFARS and its sub scores across 3 years was the outcome measure analyzed at 0, 1, 2, and 3 year visits. Each subsection has a minimum score of 0, indicating minimal effect for that component. Maximum values per section vary based on the tasks performed in each subsection; a higher score indicates greater dysfunction on that component. | Among 108 individuals enrolled,19 were excluded from the analysis population for one or more concurrent reasons. These included missing mFARS data (baseline or follow-up, n = 6), early disease stage (n = 3, mFARS baseline values 1, 7, 12.3), and inability to ambulate at baseline (n = 13). | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline up to 36 Months |
Adverse events were not collected as part of this study. All-Cause Mortality was assessed through study completion, up to 2 years.
Adverse events were not collected as part of this study. There was one subject death on the study that was attributed to complications of their disease.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FA Children | The present study enrolled 108 children aged 6.7 to 18y with genetically confirmed FRDA between Oct 2017 and October 2019. Twenty-three individuals withdrew from the study before the final visit. Of those, 13 were lost to follow-up, 7 were unwilling/unable to commit enough time (due to the tight visit schedule), 2 withdrew for other reasons (related to the pandemic/travelling), and 1 was unable to continue consent. Adverse events were not collected on this study. |
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Potential training effects of the repeated outcome measures as well as placebo effects might have increased variability. Varying demographic and genetic factors such as the presence of point mutations, GAA1 repeat length, age of onset and age at baseline also contribute to variability and may impact the rates of change over time. The COVID-19 epidemic also contributed to intermittent loss of data, and supplementing with virtual visits had limited value.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. David Lynch | The Children's Hospital of Philadelphia | 215-590-2242 | lynchd@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 3, 2021 | Feb 1, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005621 | Friedreich Ataxia |
| D001259 | Ataxia |
| ID | Term |
|---|---|
| D013132 | Spinocerebellar Degenerations |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| OTHER |
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Whole blood and plasma to measure frataxin protein and other present biomarkers.
Buccal cells (inner cheek cells) to measure frataxin protein levels.
| Change in 9-Hole Peg Test (9HPT) |
This test examines finger dexterity and involves placing and removing nine pegs in a pegboard and then removing them in the quickest possible time. The 9HPT has high intra- and inter-rater reliability and is the most commonly used measure of upper limb function in FA. The 9HPT was analyzed at 0, 1, 2, and 3 year visits. |
| Baseline up to 36 Months |
| Change in Timed Up and Go (TUG) Test | The Timed Up and Go (TUG) test is a timed measure during which the participant has to stand up from a chair, walk 3 meters, turn around, walk back, and sit down. The participant is asked to perform the task as fast and as safe as possible. The TUG is a norm-referenced measure that has established reliability for quickly assessing functional ambulatory mobility and dynamic balance in adults and children. The TUG test was analyzed at 0, 1, 2, and 3 year visits. | Baseline up to 36 Months |
| Change in Berg Balance Scale (Full Length) (BBS) Score | The Berg Balance Scale (BBS) is a widely used assessment to determine a person's balance abilities. The BBS includes a 14-item scale with static and dynamic activities of varying difficulty. The overall change in BBS score across 3 years was analyzed at 0, 1, 2, and 3 year visits. Scoring is based on a summation of the 14 item tasks scored on a five-point scale, with a range of 0-4 for each task. 0 = lowest level of function 4 = highest level of function. Highest possible score = 56 A score of < 45 indicates a greater risk of falling. | Baseline up to 36 Months |
| Change in FA-Activities of Daily Living Scale (ADL) Score | The Activities of Daily Living (ADL) assesses functional status as a measurement of the participant's ability to perform activities of daily living independently. The ADL comprises 9 questions, each question scored on a scale of 0 to 4, though participants may use increments of 0.5 if they feel they fall between two items. As with the mFARS, the total ADL score is comprised of a summation of each scored question. A minimum value of 0 on the ADL scale indicates self-evaluation of minimal effect for neurological disease components. A maximum score of 36 on the ADL indicates most severe self-evaluation of symptoms included on the survey. The overall change in ADL score across 3 years was analyzed at 0, 1, 2, and 3 year visits. | Baseline up to 36 Months |
| Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests | The Timed 1-minute Walk (T1MW) and timed 6-minute Walk are quantitative mobility and leg function performance tests based on distance traveled in one minute and six minutes. The participant is directed to one end of a clearly marked course and is instructed to walk back and forth as quickly as possible for one minute. The task is then repeated for six minutes. The distance is calculated by measuring how far the participant travels along the marked course. | Baseline up to 36 Months |
| Gainesville |
| Florida |
| 32611 |
| United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Unable to Continue Consent |
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| mFARS Total (93) | The modified Friedreich's Ataxia Rating Scale (mFARS) is a clinically validated set of assessments that measures disease progression in neurological disorder Friedreich Ataxia. The mFARS consists of four sections: bulbar (FARS A), upper limb coordination (FARS B), lower limb coordination (FARS C), and upright stability (FARS E). Minimum score of 0 in each section represents minimal disease affect. Maximum scores vary per section, with higher scores corresponding to more severe disease affect in that section. Maximum composite mFARS score 93 derived from total combined subsection scores. | Mean | Standard Deviation | units on a scale |
|
| Upright Stability (FARS E, 36) | Subsection E in the mFARS assesses upright stability as a neurologic component of Friedreich Ataxia. Minimum score of 0 represents minimal effect in upright stability. Maximum score of 36 denotes severe effect and loss of coordination to perform exam tasks. | Mean | Standard Deviation | units on a scale |
|
| Upper Limbs (FARS B, 36) | Subsection B in the mFARS assesses upper limb function as a neurologic component of Friedreich Ataxia. Minimum score of 0 represents minimal effect in upper limb coordination. Maximum score of 36 denotes severe effect and no coordination to perform exam tasks. | Mean | Standard Deviation | units on a scale |
|
| Lower Limbs (FARS C, 16) | Subsection C in the mFARS assesses lower limb function as a neurologic component of Friedreich Ataxia. Minimum score of 0 represents minimal effect in lower limb coordination. Maximum score of 16 denotes severe effect and no coordination to perform exam tasks. | Mean | Standard Deviation | units on a scale |
|
| Bulbar Function (FARS A, 5) | Subsection A in the mFARS assesses bulbar function as a neurologic component of Friedreich Ataxia. Minimum score of 0 represents minimal affect in speech or cough. Maximum score of 5 denotes severe affect and almost no useful speech and nearly absent or total loss of ability to cough. | Mean | Standard Deviation | units on a scale |
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| Secondary | Change in Timed 25-Foot Walk (T25FW) Test | The timed 25-foot walk (T25FW) test examines gait speed. The participant walks the distance of 25 feet as fast and safe as possible. Participants may use assistive devices during this task. The T25FW test was analyzed at 0, 1, 2, and 3 year visits. | Walking tests were carried out in the order: T25FW (twice), 1MW (twice), 6MW, and TUG. The T25FW, was most consistently performed at Baseline. Number of participants analyzed decreased after baseline at year 1, 2, and 3 as subjects were unable to complete the test. Reasons for not performing a test were missed visits, and, if assessment was performed, devices used. | Posted | Mean | 95% Confidence Interval | seconds | Baseline up to 36 Months |
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| Secondary | Change in 9-Hole Peg Test (9HPT) | This test examines finger dexterity and involves placing and removing nine pegs in a pegboard and then removing them in the quickest possible time. The 9HPT has high intra- and inter-rater reliability and is the most commonly used measure of upper limb function in FA. The 9HPT was analyzed at 0, 1, 2, and 3 year visits. | The number of participants analyzed decreased after baseline at years 1, 2, and 3 as subjects were unable to complete the test. Reasons for not performing a test were missed visits or refusal to complete task. | Posted | Mean | 95% Confidence Interval | seconds | Baseline up to 36 Months |
|
|
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| Secondary | Change in Timed Up and Go (TUG) Test | The Timed Up and Go (TUG) test is a timed measure during which the participant has to stand up from a chair, walk 3 meters, turn around, walk back, and sit down. The participant is asked to perform the task as fast and as safe as possible. The TUG is a norm-referenced measure that has established reliability for quickly assessing functional ambulatory mobility and dynamic balance in adults and children. The TUG test was analyzed at 0, 1, 2, and 3 year visits. | The TUG was assessed last and was performed by a higher proportion of patients vs. the 6MW. As the difficulty of the tests increased the amount of missing data increased, consistent with the progressive nature of FRDA. The number of participants analyzed decreased after baseline at years 1, 2, and 3 as subjects were unable to complete the test. Possible reasons for not performing a test were collected as "fatigue", "refused", "unable" and "unable, unrelated to disease progression". | Posted | Mean | 95% Confidence Interval | seconds | Baseline up to 36 Months |
|
|
|
| Secondary | Change in Berg Balance Scale (Full Length) (BBS) Score | The Berg Balance Scale (BBS) is a widely used assessment to determine a person's balance abilities. The BBS includes a 14-item scale with static and dynamic activities of varying difficulty. The overall change in BBS score across 3 years was analyzed at 0, 1, 2, and 3 year visits. Scoring is based on a summation of the 14 item tasks scored on a five-point scale, with a range of 0-4 for each task. 0 = lowest level of function 4 = highest level of function. Highest possible score = 56 A score of < 45 indicates a greater risk of falling. | The number of participants analyzed decreased after baseline at years 1 and 2 as subjects were unable to complete the test. Reasons for not performing a test were missed visits, and refusal to complete task. | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline up to 36 Months |
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| Secondary | Change in FA-Activities of Daily Living Scale (ADL) Score | The Activities of Daily Living (ADL) assesses functional status as a measurement of the participant's ability to perform activities of daily living independently. The ADL comprises 9 questions, each question scored on a scale of 0 to 4, though participants may use increments of 0.5 if they feel they fall between two items. As with the mFARS, the total ADL score is comprised of a summation of each scored question. A minimum value of 0 on the ADL scale indicates self-evaluation of minimal effect for neurological disease components. A maximum score of 36 on the ADL indicates most severe self-evaluation of symptoms included on the survey. The overall change in ADL score across 3 years was analyzed at 0, 1, 2, and 3 year visits. | The number of participants analyzed decreased after baseline at years 1, 2, and 3 as subjects were unable to complete the test. Reasons for not performing a test were missed visits, and refusal to complete task. | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline up to 36 Months |
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| Secondary | Change in 1-minute Walk (1MW) and 6-minute Walk (6MW) Tests | The Timed 1-minute Walk (T1MW) and timed 6-minute Walk are quantitative mobility and leg function performance tests based on distance traveled in one minute and six minutes. The participant is directed to one end of a clearly marked course and is instructed to walk back and forth as quickly as possible for one minute. The task is then repeated for six minutes. The distance is calculated by measuring how far the participant travels along the marked course. | Walking tests were carried out in the order: T25FW (twice), 1MW (twice), 6MW, and TUG. There was a notable increase in fatigue and refusals to complete the longer walking tests after the first trial of the 1MW, followed by the 6MW. As the difficulty of the tests increased the amount of missing data increased, consistent with the progressive nature of FRDA. Possible reasons for not performing a test were collected as "fatigue", "refused", "unable" and "unable, unrelated to disease progression". | Posted | Mean | 95% Confidence Interval | meters | Baseline up to 36 Months |
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| 1 |
| 89 |
| 0 |
| 0 |
| 0 |
| 0 |
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| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028361 | Mitochondrial Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| T25FW 3Y |
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| 9HPT 3Y |
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| TUG*100 3Y |
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| BBS 3Y |
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| ADL 3Y |
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| 1MW 3Y |
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| 6MW 1Y |
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| 6MW 2Y |
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| 6MW 3Y |
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