Frontotemporal Dementia Clinical Trial
Official title:
Characterization of Familial Myopathy and Paget Disease of Bone
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.
Status | Recruiting |
Enrollment | 50 |
Est. completion date | December 2026 |
Est. primary completion date | December 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
United States | University of California, Irvine | Irvine | California |
Lead Sponsor | Collaborator |
---|---|
University of California, Irvine |
United States,
Al-Obeidi E, Al-Tahan S, Surampalli A, Goyal N, Wang AK, Hermann A, Omizo M, Smith C, Mozaffar T, Kimonis V. Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy. Clin Genet. 2018 Jan;93( — View Citation
Al-Tahan S, Al-Obeidi E, Yoshioka H, Lakatos A, Weiss L, Grafe M, Palmio J, Wicklund M, Harati Y, Omizo M, Udd B, Kimonis V. Novel valosin-containing protein mutations associated with multisystem proteinopathy. Neuromuscul Disord. 2018 Jun;28(6):491-501. — View Citation
Chan N, Le C, Shieh P, Mozaffar T, Khare M, Bronstein J, Kimonis V. Valosin-containing protein mutation and Parkinson's disease. Parkinsonism Relat Disord. 2012 Jan;18(1):107-9. doi: 10.1016/j.parkreldis.2011.07.006. Epub 2011 Aug 3. — View Citation
Evangelista T, Weihl CC, Kimonis V, Lochmüller H; VCP related diseases Consortium. 215th ENMC International Workshop VCP-related multi-system proteinopathy (IBMPFD) 13-15 November 2015, Heemskerk, The Netherlands. Neuromuscul Disord. 2016 Aug;26(8):535-47 — View Citation
Fanganiello RD, Kimonis VE, Côrte CC, Nitrini R, Passos-Bueno MR. A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Braz J Med Biol Res. 2011 Apr;44(4):374-80. Epub 2011 Mar 11. R — View Citation
Farpour F, Tehranzadeh J, Donkervoort S, Smith C, Martin B, Vanjara P, Osann K, Kimonis VE. Radiological features of Paget disease of bone associated with VCP myopathy. Skeletal Radiol. 2012 Mar;41(3):329-37. doi: 10.1007/s00256-011-1193-4. Epub 2011 Jun — View Citation
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 p — View Citation
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 — View Citation
Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw C — View Citation
Kimonis V. Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia. 2007 May 25 [updated 2019 Sep 12]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): — View Citation
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. — View Citation
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 front — View Citation
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. — View Citation
Llewellyn KJ, Nalbandian A, Weiss LN, Chang I, Yu H, Khatib B, Tan B, Scarfone V, Kimonis VE. Myogenic differentiation of VCP disease-induced pluripotent stem cells: A novel platform for drug discovery. PLoS One. 2017 Jun 2;12(6):e0176919. doi: 10.1371/jo — View Citation
Llewellyn KJ, Walker N, Nguyen C, Tan B, BenMohamed L, Kimonis VE, Nalbandian A. A Fine Balance of Dietary Lipids Improves Pathology of a Murine Model of VCP-Associated Multisystem Proteinopathy. PLoS One. 2015 Jul 2;10(7):e0131995. doi: 10.1371/journal.pone.0131995. eCollection 2015. — View Citation
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 — View Citation
Mehta SG, Khare M, Ramani R, Watts GD, Simon M, Osann KE, Donkervoort S, Dec E, Nalbandian A, Platt J, Pasquali M, Wang A, Mozaffar T, Smith CD, Kimonis VE. Genotype-phenotype studies of VCP-associated inclusion body myopathy with Paget disease of bone an — View Citation
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. — View Citation
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. — View Citation
Nalbandian A, Donkervoort S, Dec E, Badadani M, Katheria V, Rana P, Nguyen C, Mukherjee J, Caiozzo V, Martin B, Watts GD, Vesa J, Smith C, Kimonis VE. The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget — View Citation
Nalbandian A, Ghimbovschi S, Radom-Aizik S, Dec E, Vesa J, Martin B, Knoblach S, Smith C, Hoffman E, Kimonis VE. Global gene profiling of VCP-associated inclusion body myopathy. Clin Transl Sci. 2012 Jun;5(3):226-34. doi: 10.1111/j.1752-8062.2012.00407.x. — View Citation
Nalbandian A, Llewellyn KJ, Gomez A, Walker N, Su H, Dunnigan A, Chwa M, Vesa J, Kenney MC, Kimonis VE. In vitro studies in VCP-associated multisystem proteinopathy suggest altered mitochondrial bioenergetics. Mitochondrion. 2015 May;22:1-8. doi: 10.1016/ — View Citation
Plewa J, Surampalli A, Wencel M, Milad M, Donkervoort S, Caiozzo VJ, Goyal N, Mozaffar T, Kimonis V. A cross-sectional analysis of clinical evaluation in 35 individuals with mutations of the valosin-containing protein gene. Neuromuscul Disord. 2018 Sep;28 — View Citation
Rodriguez-Ortiz CJ, Flores JC, Valenzuela JA, Rodriguez GJ, Zumkehr J, Tran DN, Kimonis VE, Kitazawa M. The Myoblast C2C12 Transfected with Mutant Valosin-Containing Protein Exhibits Delayed Stress Granule Resolution on Oxidative Stress. Am J Pathol. 2016 — View Citation
Shamirian S, Nalbandian A, Khare M, Castellani R, Kim R, Kimonis VE. Early-onset Alzheimers and cortical vision impairment in a woman with valosin-containing protein disease associated with 2 APOE e4/APOE e4 genotype. Alzheimer Dis Assoc Disord. 2015 Jan- — View Citation
Surampalli A, Gold BT, Smith C, Castellani RJ, Khare M, Yu H, Nguyen C, Lan M, Wencel M, Wigal S, Caiozzo V, Kimonis V. A case report comparing clinical, imaging and neuropsychological assessment findings in twins discordant for the VCP p.R155C mutation. — View Citation
Surampalli A, Khare M, Kubrussi G, Wencel M, Tanaja J, Donkervoort S, Osann K, Simon M, Wallace D, Smith C, M McInerney-Leo A, Kimonis V. Psychological Impact of Predictive Genetic Testing in VCP Inclusion Body Myopathy, Paget Disease of Bone and Frontote — View Citation
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. Epu — View Citation
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- — View Citation
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 Gene — View Citation
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. — View Citation
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 — View Citation
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. Revie — View Citation
* Note: There are 33 references in all — Click here to view all references
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05288842 -
Tanycytes in Alzheimer's Disease and Frontotemporal Dementia
|
||
Recruiting |
NCT03272230 -
Assessment of Apathy in a Real-life Situation, With a Video and Sensors-based System
|
N/A | |
Active, not recruiting |
NCT03987295 -
A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)
|
Phase 2 | |
Withdrawn |
NCT05497817 -
A Study to Evaluate Caregiver Connections Via Technology for Patients With Alzheimer's and Other Types of Dementia
|
N/A | |
Recruiting |
NCT04918251 -
EEG and TMS-based Biomarkers of ALS, MS and FTD
|
||
Completed |
NCT01002300 -
Oxytocin and Social Cognition in Frontotemporal Dementia
|
N/A | |
Completed |
NCT01890343 -
Imaging Characteristics of Florbetapir 18F in Patients With Frontotemporal Dementia, Alzheimer's Disease and Normal Controls.
|
Phase 2 | |
Completed |
NCT00376051 -
Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia
|
Phase 4 | |
Terminated |
NCT00159198 -
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
|
Phase 1 | |
Active, not recruiting |
NCT04516499 -
Neurofilament Surveillance Project (NSP)
|
||
Recruiting |
NCT04747431 -
A Study of PBFT02 in Patients With Frontotemporal Dementia and Progranulin Mutations (FTD-GRN)
|
Phase 1/Phase 2 | |
Completed |
NCT03636204 -
A First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation
|
Phase 1 | |
Completed |
NCT01937013 -
Impact of Emotional Mimicry and Oxytocin on Frontotemporal Dementia
|
Phase 2 | |
Active, not recruiting |
NCT05075187 -
Epidemiological Study in FRONtoTemporal Dementia
|
||
Not yet recruiting |
NCT05004558 -
Effects of Remote-based Resistance Training on Cardiometabolic Risk Factors, Cognitive Function, and Quality of Life in Adults Living With Alzheimer's Disease and/or Related Dementias
|
N/A | |
Completed |
NCT02999282 -
Rehabilitative Trial for the Rescue of Neurophysiological Parameters in Progranulin Deficient Subjects
|
N/A | |
Completed |
NCT00594737 -
Open Label Pilot Study of the Effects of Memantine on FDG-PET in Frontotemporal Dementia
|
Phase 3 | |
Recruiting |
NCT03225144 -
Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
|
||
Active, not recruiting |
NCT04993755 -
A Phase 2a Study of TPN-101 in Patients With C9ORF72 ALS/FTD
|
Phase 2 | |
Recruiting |
NCT04114994 -
Longitudinal Cognitive Assessment by BoCA
|