SLSMDS Natural History Study

Single Large-scale mtDNA Deletion Syndrome Natural History Study

The Single Large-Scale mtDNA Deletion Sydrome: Natural History Study (PS-NHS) aims to collect data on standardized clinical outcomes, store data on the Champ Foundation Registry (CFR) and make this data available to researchers, clinicians, and industry partners who are studying SLSMDS to answer questions regarding the disease, including its causes, potential treatments, and other topics. A secondary aim is to analyze the data to understand research questions relating to the natural history of SLSMDS.

Study Overview

• Status: Recruiting
• Conditions: Pearson Syndrome; Single Large Scale Mitochondrial DNA Deletion Syndromes (SLSMDS)

Detailed Description

This study is a prospective, observational, and longitudinal study intended to track the course of Pearson syndrome and single large scale mitochondrial DNA deletion syndromes (SLSMDS) to identify demographic, genetic, environmental, and other variables that correlate with the diseases development and outcomes. If available, retrospective clinical data may be accessed and used in analyses as well.

The PS-NHS will be conducted at two Center of Excellence sites: the Cleveland Clinic and Children's Hospital of Philadelphia (CHOP).

All PS-NHS data will be entered and stored on the CFR. The CFR exists entirely online.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44103
      • Recruiting
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients with confirmed Pearson Syndrome who satisfy the inclusion/exclusion criteria will be offered enrollment into this study.

Description

Inclusion Criteria:

• Have an active account on the Champ Foundation Registry (CFR) or be willing to create an account on the CFR.
• Must have a genetic diagnosis of a single large-scale mitochondrial DNA deletion and must upload their genetic report to the CFR.
• Have a clinical diagnosis or history of Pearson syndrome OR have symptom onset prior to five years of age and a genetic diagnosis of a single large-scale mitochondrial DNA deletion OR in the opinion of the principal investigator the participant is suitable for participating in this study based on clinical presentation.

Participants may be of any age or gender, and originate from any country.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Columbia Neurological Scale	The Columbia Neurological Scale is a neurological assessment that includes a general medical exam and a general neurological exam. It will take approximately 30 minutes to complete, and that includes evaluation of nerves, muscles and movement. Columbia Neurological Scale ranges from 0 (abnormal exam) to 76 (normal exam).	2 years
PEDI-CAT assessment	The PEDI-CAT is a computerized test that will ask participants about daily life tasks. This assessment will be given to patients 0 to 20 years old and will take approximately 15 minutes to complete.	2 years
International Pediatric Mitochondrial Disease Scale	The International Pediatric Mitochondrial Disease Scale is designed to monitor general disease progression associated with mitochondrial disease in children 0 to 18 years old. It includes a physical examination and evaluation of symptoms and functioning. The International Pediatric Mitochondrial Disease Scale will include a clinician-administered assessment that involves asking participants questions and evaluating participants' movements and responses, as well as a patient survey. The score is expressed as the percentage of items which were feasible to perform. Asterixes (*) can be scored as well, the total score will change accordingly. E.g. if the parents are not able to indicate the presence of headache, the maximum score of the first domain changes from 103 to 73. If the child is not cooperative during the execution of domain 2 and 3, these items are omitted from the total score.	2 years
Scale for Assessment and Rating of Ataxia	the SARA is a physical exam that evaluates symptoms of incoordination. A physician will complete this with exam and it will take approximately 20 minutes to complete.	2 years
Balance test	Standing balance test. May assessed with an accelerometer. Measured as time in seconds.	2 years
Coordination test	9-hold peg test. Measured as time in seconds.	2 years
2 or 6 minute walk test	2-minute walk test (2MWT) ages 3-6 yrs. or 6MWT (ages 6+). Measured as distance in meters.	2 years
Strength test	Hand grip with Dynamometer. Measured as average value of lbs of grip strength.	2 years
Hearing testing	Assessing hearing frequency in both ears.	2 years
EKG rhythm		2 years
EKG PR interval		2 years
EKG QRS interval		2 years
Echo	Assessing valve abnormalities	2 years
BNP	Measured as pg/ml	2 years
Lipid panel	Total cholesterol, HDL-C, LDL-C, triglycerides. Measured as mg/dL.	2 years
Cortisol	Measured mcg/dL	2 years
PTH	Measured as pg/mL	2 years
Calcium	Measured as pg/mL	2 years
Vitamin D	Measured ng/mL	2 years
Growth hormone	Measured ng/mL	2 years
IGF1	Measured ng/mL	2 years
TSH	Measured uIUg/mL	2 years
FT4 and T3	Measured ng/dL	2 years
HbA1c	Measured as a percentage	2 years
C-peptide	Measured ng/mL	2 years
Fasting Plasma Glucose (FPG)	Measured mg/dL	2 years
Fructosamine	Measured mcmol/L	2 years
Amylase	Measured U/L	2 years
Comprehensive Metabolic Panel	Electrolytes, transaminases, TP/Albumin, bilirubin, alk phos, creatinine, BUN, GFR. Measured mmol/L.	2 years
Lipase	Measured U/L	2 years
PT/PTT	Measured in seconds	2 years
Stool elastase	ug Elastase/g stool	2 years
Height	Assessed in cm	2 years
Weight	Assessed in kg	2 years
Orbitofrontal cortex (OFC)	Assessed in cm	2 years
Complete blood count with differential		2 years
Ferritin	Measured in ng/mL	2 years
Iron	Measured ug/dL	2 years
Reticulocytes	Count (x10^9/uL)	2 years
Reticulocytes	Percentage	2 years
Number of transfusions	Frequency count of number of red blood transfusions and platelet transfusions	2 years
Acylcarnitines (plasma)	Measured as mcmol/L	2 years
Amino acids (plasma and urine)	Interpretation recorded.	2 years
Organic acids (urine)	Interpretation recorded.	2 years
Lactate	measured mmol/L	2 years
Glutathione	Measured uM	2 years
GDF15	pg/mL	2 years
Visual exam	Assessing palpebral fissure in mm; distance in mm; eye movement in mm	2 years
ERG/OCT	Assessed as normal or abnormal	2 years
Ptosis/ophthalmoplegia	Assessed in mm	2 years
Cystatin C	Measured mg/dL	2 years
Magnesium	Measured mg/dL	2 years
Phosphate	Measured mg/dL	2 years
Urine Electrolytes	Measured mg/dL	2 years
Urine protein	Measured mg/dL	2 years
Urine amino acids		2 years
Facial dysmorphology assessment	Assessed with facial photography. Assessing ptosis and/or prominent cheeks/jowls.	2 years

Collaborators and Investigators

• Sponsor: The Champ Foundation
• Collaborators: Children's Hospital of Philadelphia; The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 16, 2021
• Primary Completion (ANTICIPATED): October 16, 2024
• Study Completion (ANTICIPATED): October 16, 2024

Study Registration Dates

• First Submitted: August 11, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (ACTUAL): September 1, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome
• Other Study ID Numbers: CFR-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data obtained during the study may be available on reasonable request.

Drug and device information, study documents

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