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

Sponsor

University Hospital Tuebingen (Other)

Overall Status

Recruiting

CT.gov ID

NCT02588638

Collaborator

(none)

100

Enrollment

Location

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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:

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

Condition or Disease	Intervention/Treatment	Phase
Movement Disorder Cognitive Decline

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:

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

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

100 participants

Observational Model:

Other

Time Perspective:

Other

Official Title:

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

Actual Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Adult patients Unclear movement disorder, unclear cognitive decline
Patients < 18 years Patients with (penetrating) suspected cerebral neurogenetic diseases

Outcome Measures

Primary Outcome Measures

Number of diagnoses made by next gereration sequency (NGS) [Within the study period of 18 months]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

For patients> 18 years

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

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

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

For patients <18 years

injury brain disorders

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

Inflammatory brain disorders

On the basis of imaging
On the basis of laboratory parameters (Oligoclonal fractions, cerebrospinal fluid (CSF) cell count increased)

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)
Sudden , abrupt beginning
Next-generation sequencing (NGS) also in the form of a panel