A Study to Assess Variation in Potential Biomarkers in Friedreich Ataxia

To test the variability of specific ribonucleic acid (RNA) and proteins as well as frataxin levels in samples of blood and buccal cells taken directly from patients with Friedreich's ataxia (FRDA) in order to confirm potential new biomarkers of disease in patients with FRDA.

Study Overview

• Status: Completed
• Conditions: Friedreich Ataxia
• Intervention / Treatment: Diagnostic test: Buccal Swabs and Blood Draws

Detailed Description

Primary Objective:

The primary objective of this study is to identify whether frataxin levels and specific RNAs and proteins in blood and buccal cells differ between patients with FRDA and controls.

Secondary Objective:

The secondary objectives of this study are:

• To understand the variability of frataxin and specific RNAs and proteins identified in buccal cells.
• To correlate levels of frataxin and specific RNAs and proteins with features of FRDA.
• To correlate levels of frataxin and specific RNAs and proteins with triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) levels, and other lipids.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

FRDA patients will be recruited using the Principal Investigator's (PI's) clinical practice.

Control patients will be obtained through family members or friends of affected individuals, as well as non-FRDA patients in the PI's practice.

Description

Inclusion Criteria:

1. Male and female patients with FRDA confirmed by genetic testing (FRDA subjects only).
2. Children and adults between the ages of 12 and 65 (inclusive); age for controls will be +/- 2 years relative to FRDA subjects.
3. Subject (and/or parent/legal guardian) has voluntarily signed consent form.
4. Willingness and ability to comply with all study procedures.
5. Functional Disability Stage (FDS) of 3, 4, or 5 (FRDA subjects only).

Exclusion Criteria:

1. Treatment with an investigational product within 30 days of study.
2. Use of gamma interferon or receiving any dose of gamma interferon within 90 days of the specimen collection day.
3. Use of any statin medications within 90 days of the specimen collection day.
4. Use of any lipid-lowering agents within 6 weeks of the specimen collection day.
5. Use of daily biotin supplementation that exceeds 30 mcg/day, either as part of a multivitamin or as a standalone supplement, within 7 days of the study visit.
6. Pregnant women.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
FRDA Subjects; Male and female subjects with FRDA confirmed by genetic testing (aim for a 50:50 distribution of males to females)	Diagnostic test: Buccal Swabs and Blood Draws; Buccal Swabs - Frataxin & specific RNA markers Blood Draws - Lipid panel, Uric Acid, Protein Marker Analysis and PAX Gene RNA Analysis
Controlled Subjects; Male and female control subjects (matched by age [+/- 2 years] and sex)	Diagnostic test: Buccal Swabs and Blood Draws; Buccal Swabs - Frataxin & specific RNA markers Blood Draws - Lipid panel, Uric Acid, Protein Marker Analysis and PAX Gene RNA Analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in frataxin levels, specific RNAs and proteins	Difference in frataxin levels, specific RNAs and proteins between FRDA patients and control patients.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variability in frataxin levels, specific RNAs and proteins	Variability in frataxin levels, specific RNAs and proteins between FRDA patients and control patients.	1 day
Correlation of frataxin levels, specific RNAs and proteins in FRDA patients	Correlation of frataxin levels, specific RNAs and proteins with features of FRDA in patients with FRDA.	1 day
Correlation of frataxin levels, specific RNAs and proteins	Correlation of frataxin levels, specific RNAs and proteins with triglycerides, HDL, LDL and other lipid levels between FRDA patients and control patients.	1 day

Collaborators and Investigators

• Sponsor: Larimar Therapeutics, Inc.
• Collaborators: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: David Lynch, M.D., Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Coppola G, Burnett R, Perlman S, Versano R, Gao F, Plasterer H, Rai M, Sacca F, Filla A, Lynch DR, Rusche JR, Gottesfeld JM, Pandolfo M, Geschwind DH. A gene expression phenotype in lymphocytes from Friedreich ataxia patients. Ann Neurol. 2011 Nov;70(5):790-804. doi: 10.1002/ana.22526.
• Coppola G, Marmolino D, Lu D, Wang Q, Cnop M, Rai M, Acquaviva F, Cocozza S, Pandolfo M, Geschwind DH. Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARgamma pathway as a therapeutic target in Friedreich's ataxia. Hum Mol Genet. 2009 Jul 1;18(13):2452-61. doi: 10.1093/hmg/ddp183. Epub 2009 Apr 17.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 14, 2020
• Primary Completion (ACTUAL): June 30, 2020
• Study Completion (ACTUAL): June 30, 2020

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (ACTUAL): February 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 17, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia; Friedreich Ataxia
• Other Study ID Numbers: CLIN-1601-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No