Familial Dementia With Neuroserpin Inclusion BodiesNCT00006176
Clinical and Genetic Studies of Familial Presenile Dementia With Neuronal Inclusion Bodies
An observational study of Familial Dementia With Neuroserpin Inclusion Bodies and Nervous System Heredodegenerative Disorder, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
The purpose of this study is to learn more about the medical problems and the genetic factors involved in a recently defined form of inherited dementia called "familial dementia with neuroserpin inclusion bodies (FDNIB)." Abnormal substances in nerve cells of patients with this disease affect brain and nervous system… Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Familial Dementia With Neuroserpin Inclusion Bodies, Nervous System Heredodegenerative Disorder
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Aug 2000to 4 Aug 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with a family history of early-onset progressive dementia or decline in cognition and neuronal inclusion bodies which are immunohistopathologically consistent with neuroserpin inclusion bodies.
- Children with progressive dementia and myoclonic epilepsy which is consistent with the reported clinical course in pediatric patients or children with the clinical phenotype who on autopsy demonstrate neuronal inclusion boidies which are immunohistopathologically consistent with neuroserpin inclusion bodies.
- Family members at risk, of at least 18 years of age, including first degree relatives of affected patients and the adult offspring of these first degree relatives.
- In rare instances probands and their at risk family members with known presenile dementia and a neurologic course typical of that seen in FENIB will be enrolled.
- We may also enroll offsite individuals who have any of the above findings, but are too medically fragile to travel to the Clinical Center and for whom a durable power of attorney (DPA) is available. The physical examination and laboratory research studies will be performed by the Investigator(s) and all clinical studies will be done in a local accredited hospital.
- Family members either not at risk and unaffected spouses may enroll primarily for genetic linkage information. These individuals will contribute a blood sample for molecular analysis only. Those unwilling to travel may also provide a blood sample only. No clinical studies will be performed on individuals from this category.
Who cannot join
- Another diagnosis of presenile demential is made by a physician including but not limited to: 1) Huntington Disease, 2) Parkinson Disease/Diffuse Lewy Body Disease, 3) Familial Alzheimer Disease with known mutations in presenilin 1, presenilin 2 or beta-amyloid precursor protein, 4) Lafora Body Disease, 5) Pick's Disease, and 6) fronto-temporal dementia.
- A Durable Power of Attorney is not available in a human subject that is not medically competent to give consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Clinical, Molecular and Biochemical Characterization of Familial Encephalopathy With Neuroserpin Inclusion Bodies
The purpose of this study is to learn more about the medical problems and the genetic factors involved in a recently defined form of inherited dementia called "familial dementia with neuroserpin inclusion bodies (FDNIB)." Abnormal substances in nerve cells of patients with this disease affect brain and nervous system function, causing confusion, memory decline and impaired cognition (thinking ability). Patients also develop movement disorders and, possibly, seizures. Symptoms begin in midlife, between 45 and 55 years of age.
Patients with FDNIB and family members 18 years of age or older at risk for the disease may be eligible for this 3-year study.
Read more
Participants will have a medical and family history and review of medical records; interview with a medical geneticist (specialist in genetics); physical, neurological and psychiatric examinations; and the following tests and procedures:
- Blood tests to assess general health
- Chest and skull X-rays
- Electrocardiogram (EKG)-record of the electrical activity of the heart using electrodes placed on the chest
- Electroencephalogram (EEG)-record of the electrical activity of the brain using electrodes placed on the head
- Ultrasound of the abdomen-imaging of abdominal organs using sound waves
- Brain magnetic resonance imaging (MRI)-imaging of the brain using a strong magnetic field and radio waves
- Hearing evaluation
- Assessment of performance of daily living activities
- Single photon emission computed tomography (SPECT)-imaging of brain metabolism and blood flow using a radioactive substance injected into a vein
The evaluation will be done over a 3- to 4-day period. At their completion, participants will meet with a physician and a genetics counselor to discuss the clinically significant findings. Participants may be asked to return for follow-up evaluations every 6 months to a year (depending on the individual's condition) for 3 years.
Read the detailed description
This project involves the study of a novel familial neurodegenerative disorder, familial encephalopathy with neuroserpin inclusion bodies (FENIB). This disorder, which has a characteristic clinical course of progressive dementia and neurologic involvement, was initially defined in one extended family. Neuroserpin is the gene for this disorder and a mutation is present in this large kindred and four additional families/cases. This protocol will characterize the clinical phenotype, delineate the natural history of the disorder and explore genotype/phenotype correlations in the index family and possibly in other reported cases. Families with immunohistopathologically-neuroserpin positive neuronal inclusions on autopsy/biopsy in an affected member(s), neuroserpin mutation-positive proband, or with familial presenile dementia with neurologic features consistent with the original FENIB family will be enrolled.
- Conditions
- Familial Dementia With Neuroserpin Inclusion Bodies, Nervous System Heredodegenerative Disorder
- Keywords
- FENIB, Presenile Dementia, Progressive Myoclonic Epilepsy, Dementia, Early Onset Progressive Dementia, Familial Presenile Dementia, FDNIB, familial encephalopathy with neuroserpin inclusion bodies, Heredodegenerative Disorders, Nervous System
- Medical subject headings
- Familial encephalopathy with neuroserpin inclusion bodies, Heredodegenerative Disorders, Nervous System, Alzheimer Disease, Myoclonic Epilepsies, Progressive, Dementia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2000 (estimated)
- Study start10 Aug 2000
- Primary completion4 Aug 2009
- Study completion4 Aug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Familial Dementia With Neuroserpin Inclusion BodiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 100 participants
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006176
- Sponsor's protocol ID
- 000191
- Other IDs
- 00-HG-0191
- Status last verified
- 4 Aug 2009
- First submitted
- 12 Aug 2000
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Davis RL, Shrimpton AE, Holohan PD, Bradshaw C, Feiglin D, Collins GH, Sonderegger P, Kinter J, Becker LM, Lacbawan F, Krasnewich D, Muenke M, Lawrence DA, Yerby MS, Shaw CM, Gooptu B, Elliott PR, Finch JT, Carrell RW, Lomas DA. Familial dementia caused by polymerization of mutant neuroserpin. Nature. 1999 Sep 23;401(6751):376-9. doi: 10.1038/43894.
PubMed 10517635Davis RL, Shrimpton AE, Carrell RW, Lomas DA, Gerhard L, Baumann B, Lawrence DA, Yepes M, Kim TS, Ghetti B, Piccardo P, Takao M, Lacbawan F, Muenke M, Sifers RN, Bradshaw CB, Kent PF, Collins GH, Larocca D, Holohan PD. Association between conformational mutations in neuroserpin and onset and severity of dementia. Lancet. 2002 Jun 29;359(9325):2242-7. doi: 10.1016/S0140-6736(02)09293-0.
PubMed 12103288Davis RL, Holohan PD, Shrimpton AE, Tatum AH, Daucher J, Collins GH, Todd R, Bradshaw C, Kent P, Feiglin D, Rosenbaum A, Yerby MS, Shaw CM, Lacbawan F, Lawrence DA. Familial encephalopathy with neuroserpin inclusion bodies. Am J Pathol. 1999 Dec;155(6):1901-13. doi: 10.1016/S0002-9440(10)65510-1.
PubMed 10595921
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical, Molecular and Biochemical Characterization of Familial Encephalopathy With Neuroserpin Inclusion Bodies
- ClinicalTrials.gov ID
- NCT00006176
- Acronym / sponsor ID
- 000191
- Conditions
- Familial Dementia With Neuroserpin Inclusion Bodies, Nervous System Heredodegenerative Disorder
- Keywords
- FENIB, Presenile Dementia, Progressive Myoclonic Epilepsy, Dementia, Early Onset Progressive Dementia, Familial Presenile Dementia, FDNIB, familial encephalopathy with neuroserpin inclusion bodies
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 10 Aug 2000
- Primary completion
- 4 Aug 2009 (actual)
- Study completion
- 4 Aug 2009 (actual)
- First posted
- 14 Aug 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn more about the medical problems and the genetic factors involved in a recently defined form of inherited dementia called "familial dementia with neuroserpin inclusion bodies (FDNIB)." Abnormal substances in nerve cells of patients with this disease affect brain and nervous system function, causing confusion, memory decline and impaired cognition (thinking ability). Patients also develop movement disorders and, possibly, seizures. Symptoms begin in midlife, between 45 and 55 years of age.
Patients with FDNIB and family members 18 years of age or older at risk for the disease may be eligible for this 3-year study.
Participants will have a medical and family history and review of medical records; interview with a medical geneticist (specialist in genetics); physical, neurological and psychiatric examinations; and the following tests and procedures:
- Blood tests to assess general health
- Chest and skull X-rays
- Electrocardiogram (EKG)-record of the electrical activity of the heart using electrodes placed on the chest
- Electroencephalogram (EEG)-record of the electrical activity of the brain using electrodes placed on the head
- Ultrasound of the abdomen-imaging of abdominal organs using sound waves
- Brain magnetic resonance imaging (MRI)-imaging of the brain using a strong magnetic field and radio waves
- Hearing evaluation
- Assessment of performance of daily living activities
- Single photon emission computed tomography (SPECT)-imaging of brain metabolism and blood flow using a radioactive substance injected into a vein
The evaluation will be done over a 3- to 4-day period. At their completion, participants will meet with a physician and a genetics counselor to discuss the clinically significant findings. Participants may be asked to return for follow-up evaluations every 6 months to a year (depending on the individual's condition) for 3 years.
Detailed description
This project involves the study of a novel familial neurodegenerative disorder, familial encephalopathy with neuroserpin inclusion bodies (FENIB). This disorder, which has a characteristic clinical course of progressive dementia and neurologic involvement, was initially defined in one extended family. Neuroserpin is the gene for this disorder and a mutation is present in this large kindred and four additional families/cases. This protocol will characterize the clinical phenotype, delineate the natural history of the disorder and explore genotype/phenotype correlations in the index family and possibly in other reported cases. Families with immunohistopathologically-neuroserpin positive neuronal inclusions on autopsy/biopsy in an affected member(s), neuroserpin mutation-positive proband, or with familial presenile dementia with neurologic features consistent with the original FENIB family will be enrolled.
Study design
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with a family history of early-onset progressive dementia or decline in cognition and neuronal inclusion bodies which are immunohistopathologically consistent with neuroserpin inclusion bodies.
- Children with progressive dementia and myoclonic epilepsy which is consistent with the reported clinical course in pediatric patients or children with the clinical phenotype who on autopsy demonstrate neuronal inclusion boidies which are immunohistopathologically consistent with neuroserpin inclusion bodies.
- Family members at risk, of at least 18 years of age, including first degree relatives of affected patients and the adult offspring of these first degree relatives.
- In rare instances probands and their at risk family members with known presenile dementia and a neurologic course typical of that seen in FENIB will be enrolled.
- We may also enroll offsite individuals who have any of the above findings, but are too medically fragile to travel to the Clinical Center and for whom a durable power of attorney (DPA) is available. The physical examination and laboratory research studies will be performed by the Investigator(s) and all clinical studies will be done in a local accredited hospital.
Key exclusion criteria (2 listed)
- Another diagnosis of presenile demential is made by a physician including but not limited to: 1) Huntington Disease, 2) Parkinson Disease/Diffuse Lewy Body Disease, 3) Familial Alzheimer Disease with known mutations in presenilin 1, presenilin 2 or beta-amyloid precursor protein, 4) Lafora Body Disease, 5) Pick's Disease, and 6) fronto-temporal dementia.
- A Durable Power of Attorney is not available in a human subject that is not medically competent to give consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10517635Davis RL, Shrimpton AE, Holohan PD, Bradshaw C, Feiglin D, Collins GH, Sonderegger P, Kinter J, Becker LM, Lacbawan F, Krasnewich D, Muenke M, Lawrence DA, Yerby MS, Shaw CM, Gooptu B, Elliott PR, Finch JT, Carrell RW, Lomas DA. Familial dementia caused by polymerization of mutant neuroserpin. Nature. 1999 Sep 23;401(6751):376-9. doi: 10.1038/43894.
- Background: PubMed 12103288Davis RL, Shrimpton AE, Carrell RW, Lomas DA, Gerhard L, Baumann B, Lawrence DA, Yepes M, Kim TS, Ghetti B, Piccardo P, Takao M, Lacbawan F, Muenke M, Sifers RN, Bradshaw CB, Kent PF, Collins GH, Larocca D, Holohan PD. Association between conformational mutations in neuroserpin and onset and severity of dementia. Lancet. 2002 Jun 29;359(9325):2242-7. doi: 10.1016/S0140-6736(02)09293-0.
- Background: PubMed 10595921Davis RL, Holohan PD, Shrimpton AE, Tatum AH, Daucher J, Collins GH, Todd R, Bradshaw C, Kent P, Feiglin D, Rosenbaum A, Yerby MS, Shaw CM, Lacbawan F, Lawrence DA. Familial encephalopathy with neuroserpin inclusion bodies. Am J Pathol. 1999 Dec;155(6):1901-13. doi: 10.1016/S0002-9440(10)65510-1.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Familial Dementia With Neuroserpin Inclusion Bodies and Nervous System Heredodegenerative Disorder, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006176, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.