Next Generation Sequencing Diagnostics - On the Road to Rapid Diagnostics for Rare Diseases (NextGen-SE)

In the study, NextGen SE are on-hand a cohort comprising each 50 pediatric and 50 adult patients, and in which there are an unclear movement disorder or an unclear cognitive disorder, examines the following questions :

Primary:

• Number of diagnoses made by NGS

Secondary:

1. restriction of the quality of life by unclear disease
2. Cost of not purposeful preliminary diagnostics ( beyond the minimal diagnostic data set )
3. Impact of the diagnosis to therapy and follow-up examinations
4. Time to diagnosis

Study Overview

• Status: Recruiting
• Conditions: Cognitive Decline; Movement Disorder

Detailed Description

In the study NextGen SE (single-center, prospective, open diagnostic study) are on-hand a cohort comprising each 50 pediatric and 50 adult patients, and in which there are an unclear movement disorder or an unclear cognitive disorder, examines the following questions:

Primary:

• Number of diagnoses made by next-generation sequencing (NGS)

Secondary:

1. Restriction of the quality of life by unclear disease
2. Cost of not purposeful preliminary diagnostics (beyond the minimal diagnostic data of the diagnosis to therapy and follow-up examinations
3. Time to diagnosis

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Ludger Schöls, Prof. Dr.; Phone Number: +49 7071 29-80445; Email: ludger.schoels@uni-tuebingen.de
• Study Contact Backup: Name: Janine Magg, Dr.; Phone Number: +49 7071 29-80445; Email: janine.magg@med.uni-tuebingen.de

Study Locations

• Germany
  • Baden-Württemberg
    • Tubingen, Baden-Württemberg, Germany, 72076
      • Recruiting
      • University Hospital
      • Contact: Ludger Schöls, Prof. Dr.; Phone Number: +49 7071 29 80445; Email: ludger.schoels@uni-tuebingen.de
      • Contact: Janine Magg, Dr.; Phone Number: +49 7071 29 80445; Email: janine.magg@med.uni-tuebingen.de
      • Principal Investigator: Ludger Schöls, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with unclear diagnoses

Description

Inclusion Criteria:

For patients> 18 years

1. Unclear movement disorder

   o Progressive ataxia after minimal exclusion diagnostics: magnetic resonance tomography (MRT) (structural lesions such as cerebellar tumor, malformation) Laboratory (Vitamin B12, thyroid peroxidase (TPO) antibodies, glutamate decarboxylase (GAD) II-antibodies (AK) In medullary lesions: Liquor exclusion Friedreich ataxia (FRDA) and spinocerebellar ataxia type (SCA)1-2-3-6

   o Progressive para-spasticity by minimal exclusion diagnostics: MRT neuro axis (structural lesions such as cervical myelopathy) Laboratory (Vitamin B12, human T-cell lymphotrophic virus ((HTLV)-AK) In medullary lesions: Liquor

2. Unclear cognitive decline o After minimal exclusion diagnosis MRT (intracranial pressure, focal brain lesions explanatory) laboratory (Thyroid-stimulating hormone (TSH), TPO-AK, antibody profile limbic encephalitis) Liquor (inflammation, meningitis) Electroencephalography (EEG) (Status) Exclusion chromosome 9 open reading frame 72 (C9orf72)

For patients <18 years Patients with (penetrating) suspected cerebral neurogenetic diseases

• Unclear movement disorder (spasticity, ataxia, dyskinesia)
• Unclear cognitive disorder with probability of monogenic origin
• Fragile X Syndrome (Fra-X) at mentally retarded boy, Friedreich ataxia (FRDA) with ataxia should be genetically excluded

Exclusion Criteria:

For patients > 18 years

1. Lack of consent
2. symptom onset > 40 years of age
3. Sudden, abrupt beginning
4. As early as previous history of genetic diagnosis using next-generation sequencing (NGS), also in the form of a panel

For patients <18 years

1. injury brain disorders

   • On the basis of imaging
   • On the basis of medical history (premature baby, hypoxic-ischemic encephalopathy)

2. Inflammatory brain disorders

   • On the basis of imaging
   • On the basis of laboratory parameters (Oligoclonal fractions, cerebrospinal fluid (CSF) cell count increased)
3. Light, isolated mental developmental disorder or behavioral disorder (rare monogenetic) - (less than 2 standard deviartion of normal or - < 6 year olds - less than 1 year in development history back)
4. Sudden , abrupt beginning
5. Next-generation sequencing (NGS) also in the form of a panel

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Adult patients; Unclear movement disorder, unclear cognitive decline
Patients < 18 years; Patients with (penetrating) suspected cerebral neurogenetic diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of diagnoses made by next gereration sequency (NGS)	Within the study period of 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Restriction of the quality of life by unclear disease measured rated by Quality of Life Questionnaire (EQ5D), Depression Questionnaire (PHQ)	EQ-5D: Calculation preference value PHQ: Categorical analysis carried out by modified evaluation algorithms of the Diagnostic and Statistical Manual of Mental Disorders (DSM) -IV B	At day 1
Cost of not purposeful preliminary diagnostics rated by questionnaire on costs (number of outpatient performances, stationary investigations, repetition 's imaging, genetic single diagnostics, high-priced diagnostic		At day 1
Time to diagnosis	For patients whose diagnosis can be made by NGS	At day 1

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Ludger Schöls, Prof. Dr., University Hospital Tübingen

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 26, 2015
• First Posted (Estimate): October 28, 2015

Study Record Updates

• Last Update Posted (Actual): November 13, 2020
• Last Update Submitted That Met QC Criteria: November 11, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Quality of life; Diagnosis; NGS; Rare disease; Next-generation sequencing
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Disease Attributes; Cognition Disorders; Cognitive Dysfunction; Movement Disorders; Rare Diseases
• Other Study ID Numbers: NextGen-SE