Characterization of Inclusion Body Myopathy Associated With Paget's Disease of Bone and Frontotemporal Dementia (IBMPFD) - Full Text View

Purpose

The investigators are researching families with inherited inclusion body myopathy (IBM) and/or Paget disease of bone (PDB) and/or dementia (FTD) which is also called IBMPFD. IBMPFD is caused by mutations in the VCP gene. Our main goal is to understand how changes in the VCP gene cause the muscle, bone and cognitive problems associated with the disease.

The investigators are collecting biological specimen such as blood and urine samples, family and medical histories, questionnaire data of patients with a personal or family history of VCP associated disease. Participants do not need to have all symptoms listed above in order to qualify. A select group of participants may be invited to travel to University of California, Irvine for a two day program of local procedures such as an MRI and bone scan.

Samples are coded to maintain confidentiality. Travel is not necessary except for families invited for additional testing.

Condition
Inclusion Body Myopathy With Early-onset Paget Disease and Frontotemporal Dementia Paget Disease of Bone Frontotemporal Dementia Myopathy


Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Cross-Sectional
Official Title:	Characterization of Familial Myopathy and Paget Disease of Bone

Resource links provided by NLM:

Genetics Home Reference related topics: CHMP2B-related frontotemporal dementia GRN-related frontotemporal dementia Paget disease of bone frontotemporal dementia with parkinsonism-17 inclusion body myopathy with early-onset Paget disease and frontotemporal dementia juvenile Paget disease

MedlinePlus related topics: Bone Diseases Dementia Muscle Disorders Paget's Disease of Bone

Genetic and Rare Diseases Information Center resources: Primary Progressive Aphasia Frontotemporal Dementia Frontotemporal Dementia, Ubiquitin-positive Pick's Disease Semantic Dementia Familial Alzheimer Disease

U.S. FDA Resources

Further study details as provided by University of California, Irvine:

Biospecimen Retention: Samples With DNA

Whole blood, skin and muscle biopsy, urine sample, if available samples obtained from previous diagnostic evaluations such as muscle biopsy.


Estimated Enrollment:	50
Study Start Date:	January 2000
Estimated Primary Completion Date:	December 2025 (Final data collection date for primary outcome measure)

Groups/Cohorts
VCP families Patients with a personal or family history of VCP associated disease.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Individuals with a personal or family history of VCP associated disease.

Criteria

Inclusion Criteria:

Inclusion criteria include all individuals with a combination of medical problems including muscle and bone disease and their family members. Because historically VCP related muscle disease has been erroneously diagnosed with the following diagnoses, therefore if these patients also have a personal or family history of bone disease they will be considered eligible for the study:

Muscle disorders considered include:

Limb Girdle Muscular Dystrophy
Myopathy
Inclusion body myopathy
FSH (Facioscapular muscular dystrophy) without the mutation
Scapuloperoneal muscular dystrophy
Amyotrophic Lateral Sclerosis
Non specific muscular dystrophy

AND

Bone disorders including:
- Paget disease of bone
- Fibrous dysplasia
- Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH)
- Non-specific bone disease

Eligible participants must also be:

Subjects must to 18 years or older
Subjects must to able to give consent
Adult family members or spouses over the age of 18 of the affected individuals

Exclusion Criteria:

Under the age of 18.

Individuals who report a different unrelated diagnosis will be excluded from the study. Testing to confirm different diagnoses will not be performed, instead patient will be questioned for this information and records will be obtained for confirmation of appropriate testing.

Those who are unable to provide consent for themselves will be excluded from participating in the study.

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353430

Contacts


Contact: Sandra Donkervoort, MS, CGC	949 824 0521	sdonkerv@uci.edu

Locations


United States, California
University of California, Irvine	Recruiting
Irvine, California, United States, 92697-1385
Contact: Sandra Donkervoort, MS CGC 949-824-0521 sdonkerv@uci.edu
Principal Investigator: Virginia Kimonis, MD

Sponsors and Collaborators

University of California, Irvine

Investigators


Principal Investigator:	Virginia Kimonis, MD	University of California, Irvine

More Information

Publications:

Tresse E, Salomons FA, Vesa J, Bott LC, Kimonis V, Yao TP, Dantuma NP, Taylor JP. VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy. 2010 Feb;6(2):217-27. Epub 2010 Feb 22.

Hübbers CU, Clemen CS, Kesper K, Böddrich A, Hofmann A, Kämäräinen O, Tolksdorf K, Stumpf M, Reichelt J, Roth U, Krause S, Watts G, Kimonis V, Wattjes MP, Reimann J, Thal DR, Biermann K, Evert BO, Lochmüller H, Wanker EE, Schoser BG, Noegel AA, Schröder R. Pathological consequences of VCP mutations on human striated muscle. Brain. 2007 Feb;130(Pt 2):381-93. Epub 2006 Sep 19.

Vesa J, Su H, Watts GD, Krause S, Walter MC, Martin B, Smith C, Wallace DC, Kimonis VE. Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts. Neuromuscul Disord. 2009 Nov;19(11):766-72. doi: 10.1016/j.nmd.2009.08.003. Epub 2009 Oct 13.

Weihl CC, Pestronk A, Kimonis VE. Valosin-containing protein disease: inclusion body myopathy with Paget's disease of the bone and fronto-temporal dementia. Neuromuscul Disord. 2009 May;19(5):308-15. doi: 10.1016/j.nmd.2009.01.009. Epub 2009 Apr 19. Review.

Kimonis VE, Mehta SG, Fulchiero EC, Thomasova D, Pasquali M, Boycott K, Neilan EG, Kartashov A, Forman MS, Tucker S, Kimonis K, Mumm S, Whyte MP, Smith CD, Watts GD. Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. Am J Med Genet A. 2008 Mar 15;146A(6):745-57. doi: 10.1002/ajmg.a.31862.

Watts GD, Thomasova D, Ramdeen SK, Fulchiero EC, Mehta SG, Drachman DA, Weihl CC, Jamrozik Z, Kwiecinski H, Kaminska A, Kimonis VE. Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Clin Genet. 2007 Nov;72(5):420-6.

Mehta SG, Watts GD, Adamson JL, Hutton M, Umberger G, Xiong S, Ramdeen S, Lovell MA, Kimonis VE, Smith CD. APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD). Genet Med. 2007 Jan;9(1):9-13.

Forman MS, Mackenzie IR, Cairns NJ, Swanson E, Boyer PJ, Drachman DA, Jhaveri BS, Karlawish JH, Pestronk A, Smith TW, Tu PH, Watts GD, Markesbery WR, Smith CD, Kimonis VE. Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations. J Neuropathol Exp Neurol. 2006 Jun;65(6):571-81.

Mehta SG, Watts GD, McGillivray B, Mumm S, Hamilton SJ, Ramdeen S, Novack D, Briggs C, Whyte MP, Kimonis VE. Manifestations in a family with autosomal dominant bone fragility and limb-girdle myopathy. Am J Med Genet A. 2006 Feb 15;140(4):322-30.

Kimonis VE, Watts GD. Autosomal dominant inclusion body myopathy, Paget disease of bone, and frontotemporal dementia. Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19 Suppl 1:S44-7.

Lucas GJ, Mehta SG, Hocking LJ, Stewart TL, Cundy T, Nicholson GC, Walsh JP, Fraser WD, Watts GD, Ralston SH, Kimonis VE. Evaluation of the role of Valosin-containing protein in the pathogenesis of familial and sporadic Paget's disease of bone. Bone. 2006 Feb;38(2):280-5. Epub 2005 Sep 30.

Watts GD, Wymer J, Kovach MJ, Mehta SG, Mumm S, Darvish D, Pestronk A, Whyte MP, Kimonis VE. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet. 2004 Apr;36(4):377-81. Epub 2004 Mar 21.

Watts GD, Thorne M, Kovach MJ, Pestronk A, Kimonis VE. Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genes. Neuromuscul Disord. 2003 Sep;13(7-8):559-67.

Kimonis VE, Fulchiero E, Vesa J, Watts G. VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. Biochim Biophys Acta. 2008 Dec;1782(12):744-8. doi: 10.1016/j.bbadis.2008.09.003. Epub 2008 Sep 18. Review.


Responsible Party:	Dr. Virginia Kimonis, MD, University of California, Irvine
ClinicalTrials.gov Identifier:	NCT01353430 History of Changes
Other Study ID Numbers:	VK2007-5832
Study First Received:	January 26, 2011
Last Updated:	May 12, 2011

Keywords provided by University of California, Irvine:


IBMPFD - Inclusion Body Myopathy associated with Paget's disease of bone and Frontotemporal Dementia VCP gene - Valosin-containing protein gene

Additional relevant MeSH terms:


Frontotemporal Dementia Pick Disease of the Brain Dementia Alzheimer Disease Muscular Diseases Aphasia, Primary Progressive Bone Diseases Osteitis Deformans Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurocognitive Disorders Mental Disorders Tauopathies	Neurodegenerative Diseases Musculoskeletal Diseases Neuromuscular Diseases Frontotemporal Lobar Degeneration TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases Aphasia Speech Disorders Language Disorders Communication Disorders Neurobehavioral Manifestations Neurologic Manifestations Signs and Symptoms

ClinicalTrials.gov processed this record on September 21, 2017