Next Generation Sequencing Diagnostics - On the Road to Rapid Diagnostics for Rare Diseases

• Conditions: Cognitive Decline; Movement Disorder

• Registration Number: NCT02588638
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

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

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 Timeline

• Study First Submitted: 2015-10-15
• Study First Submitted QC: 2015-10-26
• Study First Posted: 2015-10-28
• Study Start: 2015-12
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-11
• Last Update Posted: 2020-11-13
• Primary Completion: 2022-06
• Study Completion: 2023-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of diagnoses made by next gereration sequency (NGS)	Within the study period of 18 months

Secondary Outcome Measures

Name	Time	Method
Restriction of the quality of life by unclear disease measured rated by Quality of Life Questionnaire (EQ5D), Depression Questionnaire (PHQ)	At day 1	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
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	At day 1	For patients whose diagnosis can be made by NGS

Trial Locations

Locations (1)

University Hospital; 🇩🇪 Tubingen, Baden-Württemberg, Germany