Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Features and Potential Etiology of Epilepsy and Nodding Syndrome in the Mahenge Area, Ulanga District (NSEC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03653975
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
Thomas Wagner, Heidelberg University

Brief Summary:

Background: Childhood epilepsy disorders are particular frequent in the area around Mahenge, southern Tanzania and recent studies have described a novel type of epilepsy with repetitive head nodding episodes and often progressive cognitive dysfunction. Despite the disease affecting thousands in Tanzania, Uganda and South Sudan, etiology and pathogenesis of the disorder termed Nodding Syndrome (NS) is still obscure as the phenotype remains imprecisely described. Epidemiological associations with Onchocerca volvulus and Mansonella spp. were noted at different African sites and remain robust even though no evidence for the presence of O. volvulus in CSF or any previous contact with the CSF was found.

Hypothesis: With regard to the complex host immune reaction to O. volvulus, the investigators hypothesize that the immune response against filariae might contribute to NS and epilepsy. The investigators further assume that specific genetic traits might play a role in the pathogenesis of NS.

Aims In the present study the investigators aim to examine if and how O. volvulus and/or Mansonella spp. contribute to the pathology of NS/epilepsy and therefore intend to analyze the filarial infection and the host immune response in affected children. To identify inherited traits predisposing for epilepsy, NS or specific immune responses, a genetic workup that includes whole-exome sequencing (WES) is performed. The clinical and EEG characteristics are further defined. Cognitive impairment of people with epilepsy and NS is assessed using the Wechsler Nonverbal Scale of Ability (WNV).

Study design: A cross-sectional observational (groups I-III) and a case-control (groups I-V) study recruiting in total 250 patients and controls (I: people with NS, n=50; II: people with epilepsy (PWE) and onchocerciasis, n=50; III: PWE without onchocerciasis, n=50; IV: controls with onchocerciasis but otherwise healthy, n= 50; healthy controls without evidence for onchocerciasis, n= 50) is performed to describe the clinical characteristics in children with NS/epilepsy and to evaluate differences in infection and immune response between groups, respectively. The WNV should be validated in 500 healthy controls to obtain reference data in rural Africa.

Summary: In summary, the study aims to elucidate clinical characteristics and the pathogenesis of NS/epilepsy in children of southern Tanzania and role of parasitic infection as a cause for NS/epilepsy.


Condition or disease Intervention/treatment
Nodding Syndrome Epilepsy Onchocerciasis Cognitive Impairment Other: no intervention

  Show Detailed Description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 250 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Clinical Features and Potential Etiology of Epilepsy and Nodding Syndrome in the Mahenge Area, Ulanga District
Actual Study Start Date : October 2014
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019


Group/Cohort Intervention/treatment
Nodding syndrome

I) probable Case of Nodding Syndrom (according to the "WHO epidemiologic surveillance case definition") *reported head nodding ** in a previously healthy person with at least 2 major and 1 minor criteria

Major criteria

  • Age 3 to 18 y at onset of head nodding
  • Nodding frequency 5 to 20 times per min

Minor criteria

  • Other neurologic abnormalities
  • Clustering in space or time with similar cases
  • Triggering by eating or cold weather
  • Delayed sexual or physical development
  • Psychiatric manifestations

    • As agreed upon at the first International Conference on Nodding Syndrome, Kampala, Uganda, July 2012 (16). ** Repetitive involuntary drops of the head toward the chest on >2 occasions.
Other: no intervention
no intervention

epilepsy and onchocerciasis

II) People with epilepsy (PWE) and onchocerciasis (n= 50)

  • confirmed or suspected generalized and idiopathic epilepsy
  • confirmed active infection with O. volvulus (microscopy, PCR and serology)

Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention
no intervention

epilepsy, no onchocerciasis

III) People with epilepsy (PWE) without onchocerciasis (n= 50)

  • confirmed or suspected generalized and idiopathic epilepsy
  • excluded active or past infection with O. volvulus (microscopy, PCR and serology)

Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention
no intervention

no epilepsy but onchocerciasis

IV) Controls with onchocerciasis, otherwise healthy (n= 50)

  • no evidence for epilepsy or other neurological diseases
  • confirmed active infection with O. volvulus (microscopy, PCR and serology)

Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention
no intervention

no epilepsy, no onchocerciasis

V) Healthy Controls without onchocerciasis (n= 50)

  • no evidence for epilepsy or other neurological diseases
  • excluded active or past infection with O. volvulus (microscopy, PCR and serology)

Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention
no intervention

controls for Wechsler Nonverbal (WNV)

Healthy Controls for cognitive assessment only, (n= 750)

no evidence for epilepsy or other neurological diseases no detailled examination on O. volvulus performed

Patients with cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.

Other: no intervention
no intervention




Primary Outcome Measures :
  1. Describing clinical features in children with Nodding Syndrome and other forms of epilepsy e.g. characteristics of the seizures, EEG abnormalities and reporting co-morbidities and impairments. [ Time Frame: 2014-2018 ]
    Obtaining clinical features and medical history. Comparing medical history, Seizure types and -frequency and other clinical Features between the groups.

  2. Describing EEG features in children with Nodding Syndrome and other forms [ Time Frame: 2014-2018 ]
    Performing EEG recordings and comparing EEG abnormalities (numbers, types and site of epileptiform discharges (ED), background alterations) between the groups.


Secondary Outcome Measures :
  1. Measuring the rate of filarial infections in patients with NS, epilepsy and controls. [ Time Frame: 2014-2018 ]
    Performing skin snip microscopy and PCR analysis to detect O. volvulus and Mansonella spp. in patients with NS, epilepsy and controls.

  2. Characterization of O. volvulus in patients with Nodding Syndrome and epilepsy. [ Time Frame: 2014-2018 ]
  3. Characterization of the host immune response to O. volvulus. [ Time Frame: 2014-2018 ]
  4. Analyzing for genetic traits associated with epilepsy, NS, enhanced Ivermectin toxicity or specific immune responses. [ Time Frame: 2014-2018 ]
    Performing a genetic workup for known monogenetic forms of epilepsy, single nucleotide polymorphisms (SNP) associated with enhanced Ivermectin toxicity and adverse immune reactions. Performing a Whole-exome sequencing (WES) with biomedical analysis.

  5. Measuring the cognitive impairment in patients with NS and epilepsy. [ Time Frame: 2014-2018 ]
    Using the Wechsler Nonverbal Scale of Ability (WNV) and comparing the results to matched healthy controls.


Biospecimen Retention:   Samples With DNA
To further describe the clinical features of NS, a complete physical and neurological examination in patients with NS and controls is performed at the Mahenge Epilepsy Clinic. All individuals will have to undergo sampling of blood and skin snips from at least two different areas of the body, one of which must be close to the head. Time expenditure for the individual participant is estimated with 60 min (Introduction of the study, consent, skin snip, lumbar puncture and venipuncture) extended for about 60 minutes if EEG recordings are obtained.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   3 Years to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

With support of the hospital staff, participants aged 3 to 99 years will be recruited consecutively among the registered patients as they are seen once a month for a clinical check-up and to receive their medication. Suitable relatives of patients will also be asked to take part in the study.

The study groups with their respective inclusion criteria are defined above. Patients of group I-III will be first recruited into the cross-sectional study and subsequently into the case-control study. Groups II to VI will be matched to Group I for age, gender, social status and stay within the Mahenge area.

Criteria

I) Patients with Nodding syndrome confirmed or suspected Case of Nodding syndrome (according to the WHO epidemiologic surveillance case definition: reported head nodding in a previously healthy person with at least 2 major and 1 minor criteria Major criteria Age 3 to 18 y at onset of head nodding Nodding frequency 5 to 20 times per min Minor criteria Other neurologic abnormalities (cognitive decrease, school dropout due to cognitive or behavioral problems, other seizures or neurologic abnormalities) Clustering in space or time with similar cases Triggering by eating or cold weather Delayed sexual or physical development Psychiatric manifestations

As agreed upon at the first International Conference on Nodding Syndrome, Kampala, Uganda, July 2012 (16). EEG,

II) People with epilepsy (PWE) and onchocerciasis confirmed or clinically suspected generalized and idiopathic epilepsy confirmed active infection with O. volvulus (microscopy, PCR and serology)

III) People with epilepsy (PWE) without onchocerciasis confirmed or clinically suspected generalized and idiopathic epilepsy excluded active or past infection with O. volvulus (microscopy, PCR and serology)

IV) Controls with onchocerciasis, otherwise healthy no evidence for epilepsy or other neurological diseases confirmed active infection with O. volvulus (microscopy, PCR and serology)

V) Controls without onchocerciasis, otherwise healthy no evidence for epilepsy or other neurological diseases excluded active or past infection with O. volvulus (microscopy, PCR and serology)

VI) Healthy controls for cognitive assessment, matched to Groups I to V

inclusion criteria: The study groups with their respective inclusion criteria are defined above.

Patients of group I-III will be first recruited into the cross-sectional study and subsequently into the case-control study. Groups II to VI will be matched to Group I for age, gender, social status and stay within the Mahenge area.

exlusion criteria: Patients with evidence for co-infections with HIV, Tb, Malaria or other parasites, cardiovascular or renal comorbidities, a history of birth or traumatic brain injuries, psychiatric comorbidities, insecure comprehension of the information given, lacking or withdrawn consent will be excluded.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03653975


Contacts
Layout table for location contacts
Contact: Thomas Wagner, MD Wagner.Thomas@rheuma-kinderklinik.de
Contact: Thomas Wagner, MD Thomasiminternet@gmx.de

Locations
Layout table for location information
Tanzania
Mahenge Epilepsy Clinic Recruiting
Mahenge, Tanzania
Contact: William Matuja, Professor         
Sponsors and Collaborators
Heidelberg University

Layout table for additonal information
Responsible Party: Thomas Wagner, MD, Heidelberg University
ClinicalTrials.gov Identifier: NCT03653975     History of Changes
Other Study ID Numbers: HD-DZIF-MUHAS
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Thomas Wagner, Heidelberg University:
Nodding Syndrome
Head Nodding
Epilepsy
Onchocerciasis
Cognitive impairment
Mahenge

Additional relevant MeSH terms:
Layout table for MeSH terms
Syndrome
Epilepsy
Cognitive Dysfunction
Onchocerciasis
Nodding Syndrome
Disease
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Filariasis
Spirurida Infections
Secernentea Infections
Nematode Infections
Helminthiasis
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Epilepsy, Generalized