Clinical trial NCT00608881: Coenzyme Q10 in Huntington's Disease (HD)
Official title: Coenzyme Q10 in Huntington's Disease (HD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Huntington's Disease
Keywords: Huntington's disease
Huntington disease
HD
coenzyme Q10
CoQ
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Rochester
First posted: 2008-02-06
Enrollment: 609
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goals of this trial are to determine if coenzyme Q10 is effective in slowing the worsening symptoms of Huntington's disease and to learn about the safety and acceptability of long-term coenzyme Q10 use by determining its effects on people with Huntington's disease.

Detailed description: Huntington's disease (HD) is a slowly progressive disorder that devastates the lives of those affected and their families. There are no treatments that slow the progression of HD, only mildly effective symptomatic therapies are available.

The purpose of this trial is to find out if coenzyme Q10 (CoQ) is effective in slowing the worsening symptoms of HD. In this study, researchers also will learn about the safety and acceptability of long-term CoQ use by determining its effects on people with HD.

Participants in this trial will be randomly chosen to one of two groups. Group 1 will receive CoQ (2400 mg/day), and group 2 will receive a placebo (an inactive substance). Researchers will compare the change in total functional capacity (TFC)-a measure of functional disability-in the two groups. The TFC is a valid and reliable measure of disease progression and is particularly responsive to change in the early and mid-stages of HD. Researchers will also compare the changes in other components of the Unified Huntington's Disease Rating Scale '99 (UHDRS) including: the total motor score, total behavioral frequency score, total behavior frequency X severity score, verbal fluency test, symbol digit modalities test, Stroop, interference test, functional checklist, and independence scale scores. The groups will also be compared with respect to tolerability, adverse events, vital signs, and laboratory test results as measures of safety.

Eligibility criteria: Inclusion Criteria:

To be eligible for enrollment into this study, subjects must meet the following eligibility criteria within 28 days prior to randomization:

* Subjects must have clinical features of HD and a confirmed family history of HD, OR a CAG repeat expansion ≥ 36.
* TFC \> 9.
* Must be ambulatory and not require skilled nursing care.
* Age ≥ 16 years.
* Women must not be able to become pregnant (e.g., post menopausal, surgically sterile or using adequate birth control methods for the duration of the study).
* If psychotropic medications are taken (e.g., anxiolytics, hypnotics, benzodiazepines, antidepressants), they must be at a stable dosage for four weeks prior to randomization and should be maintained at a constant dosage throughout the study, as possible. (Note: stable dosing of tetrabenazine is allowable.) Any changes to these medications mandated by clinical conditions will be systematically recorded and the subject will be permitted to remain in the trial.
* Able to give informed consent and comply with trial procedures
* Able to take oral medication.
* May be required to identify an informant or caregiver who will be willing and able to supervise the daily dosing of study medications and to maintain control of study medications in the home.
* A designated individual will be identified by the subject to participate in the ongoing consent process should the subject's cognitive capacity to consent become compromised during participation in the study.

Exclusion Criteria:

* History or known sensitivity of intolerability to CoQ.
* Exposure to any investigational drug within 30 days of the Baseline visit.
* Clinical evidence of unstable medical illness in the investigator's judgment.
* Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression or suicidal ideation within 90 days of the Baseline visit.
* Substance (alcohol or drug) abuse within one year of the Baseline visit.
* Women who are pregnant or breastfeeding.
* Use of supplemental coenzyme Q10 within 30 days prior to the Baseline visit
* Clinically serious abnormalities in the screening laboratory studies (Screening creatinine greater than 2.0, alanine aminotransferase (ALT) or total bilirubin greater than 3 times the upper limit of normal, absolute neutrophil count of ≤1000/ul, platelet concentration of \<100,000/ul, hematocrit level of \<33 for female or \<35 for male, or coagulation tests \> 1.5 time upper limit of normal).
* Known allergy to FD\&C yellow #5 or any other ingredient in the study drug (active and placebo)

Primary outcomes:
measure: Joint Rank (Combination of Time to Death (for Subjects Who Died) and Change in Total Functional Capacity Score (TFC) From Baseline to Month 60 (for Subjects Who Survived))
timeFrame: 5 years
Secondary outcomes:
measure: Change in Total Functional Capacity (TFC) Score From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Functional Checklist Score From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Independence Scale Score From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Total Motor Score From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Behavioral Frequency Score From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Behavioral Frequency x Severity Score From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Symbol Digit Modalities Test (SDMT) From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Verbal Fluency Test From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Stroop Interference Test - Color Naming From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Stroop Interference Test - Word Reading From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Change in Stroop Interference Test - Interference From Baseline to Month 60
timeFrame: Baseline and Month 60
measure: Time to a Two-Point Decline in TFC Score or Death
timeFrame: 5 years
measure: Time to a Three-Point Decline in TFC Score or Death
timeFrame: 5 years
measure: Number Completing Study at Assigned Dosage Level
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama At Birmingham, Pediatric Neurology Childrens, Harbor Bldg Suite 314, 1600 7Th Avenue South
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona, 13400 East Shea Boulevard, Csu-Cp21B
state: Arizona
city: Fayetteville
country: United States
facility: WASHINGTON REGIONAL MEDICAL CENTER, 3215 N. North Hills Blvd
state: Arkansas
city: Irvine
country: United States
facility: University of California Irvine, Department of Neurology, 100 Irvine Hall
state: California
city: Sacramento
country: United States
facility: University of California Davis, Medical Center Dept of Neurology, Acc Building Suite 3700, 4860 Y Street
state: California
city: Littleton
country: United States
facility: Colorado Neurological Institute, Movement Disorders Center, 701 East Hampden Avenue Suite 510
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Center for Movement Disorders and Neurorestoration, 3450 Hull Road, 4th Floor
state: Florida
city: Miami
country: United States
facility: UNIVERSITY OF MIAMI, 1150 NW 14th STREET, #401
state: Florida
city: Tampa
country: United States
facility: University of South Florida, College of Medicine Dept of Neurology, 12901 Bruce B Downs Blvd Mdc-55
state: Florida
city: Atlanta
country: United States
facility: Emory University, Wesley Woods Center, 1841 Clifton Road NE Room 314
state: Georgia
city: Boise
country: United States
facility: Idaho Elks Rehabilitation Hospital, 600 North Robbins Road
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center, Department of Neurological Sciences, 1725 West Harrison Suite 755
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine, Outpatient Clinical Research Facility, 535 Barnhill Drive Room #150
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics, 200 Hawkins Road, Room W263 General Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center, Department of Neurology, 3599 Rainbow Blvd Mail Stop 2012
state: Kansas
city: Wichita
country: United States
facility: Hereditary Neurological Disease Centre (Hndc),3223 N. Webb, Suite 4
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland School of Medicine, 22 South Greene Street, N4 W49-B
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University, 600 North Wolfe Street, Meyer 2-181
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine, Department of Neurology, 715 Albany Street C329
state: Massachusetts
city: Charlestown
country: United States
facility: Massachusetts General Hospital, 149 13Th Street Suite 2241
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, 1500 E Medical Center Drive, B1 H202 Nuclear Medicine
state: Michigan
city: Golden Valley
country: United States
facility: Struthers Parkinson'S Center, 6701 Country Club Drive
state: Minnesota
city: St Louis
country: United States
facility: Washington University School of Medicine, Box 8111, 660 South Euclid
state: Missouri
city: Las Vegas
country: United States
facility: University of Las Vegas School of Medicine, 1707 W. Charleston Blvd, Suite 220
state: Nevada
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Edison
country: United States
facility: Nj Neuroscience Institute, Jfk Medical Center, 65 James Street
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College, Parkinson'S Disease & Movement Disorders Ctr
state: New York
city: Manhasset
country: United States
facility: North Shore-Lij Health System, 350 Community Drive Room 110, Research Institute
state: New York
city: New York
country: United States
facility: Columbia University, Sergievsky Center P&S Box 16, 630 West 168Th Street
state: New York
city: Rochester
country: United States
facility: University of Rochester, Department of Neurology, 919 Westfall Road Building C Suite 220
state: New York
city: Durham
country: United States
facility: Duke University, 932 Morreene Road #213
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University, Baptist Med Center, Department of Neurology, Medical Center Boulevard
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati/Cincinnati Children'S Hospital, 222 Piedmont Avenue, Suite 3200
state: Ohio
city: Columbus
country: United States
facility: OHIO STATE UNIVERSITY , 2006 Kenny Road
state: Ohio
city: Allentown
country: United States
facility: ST. LUKE'S HOSPITAL, 240 Centronia Road
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania, Pennsylvania Hospital Department of Neurology , 330 South 9Th Street
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Kaufmann Medical Building, 3471 Fifth Avunue, Suite 811
state: Pennsylvania
city: Providence
country: United States
facility: BUTLER HOSPTIAL MOVEMENT DISORDER PROGRAM, 345 Blackstone Boulevard
state: Rhode Island
city: Memphis
country: United States
facility: The University of Tennesee Health Science Cen, 855 Monroe Avenue, Department of Neurology, Room 415 Link Bldg
state: Tennessee
city: Dallas
country: United States
facility: UN oF TEXAS SOUTHWESTERN MED CENTER DALLAS, 5323 HARRY HINES BOULEVARD H1.108
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, 6550 Fannin Suite 1801
state: Texas
city: Wentworthville
country: Australia
facility: Westmead Hospital, Department of Neurology Level 1, Po Box 533
state: New South Wales
city: Calgary
country: Canada
facility: University of Calgary, Heritage Medical Research Clinic, Trw Bldg 5 Floor, 3280 Hospital Dri. NW
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Glenrose Rehab Hosp, Movement Disorder Clinic , Rm 0601 Gleneast 10230 - 111 Avenue
state: Alberta
city: Vancouver
country: Canada
facility: Department of Medical Genetics, Ubc Hospital, Room S179-2211 Westbrook Mall
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre, University Hospital, 339 Windermere Road
state: Ontario
city: Markham
country: Canada
facility: Centre For Movement Disorders, 2780 Bur Oak Avenue
state: Ontario
city: Toronto
country: Canada
facility: NORTH YORK GENERAL HOSPITAL (2), 4001 Leslie Street
state: Ontario
city: Toronto
country: Canada
facility: North York General Hospital, 4001 Leslie Street
state: Ontario
Study officials:
affiliation: Massachusetts General Hospital
name: Merit Cudkowicz, MD MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester, Biostatistics
name: Michael McDermott, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Director, Clinical Trials Coordination Center, University of Rochester
name: Karl Kieburtz, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kowall N, Ferrante R, Martin J. Patterns of cell loss in Huntington's disease. Trends in Neurosciences 1987;10:24-29.
citation: Riley D, Lang A. Movement Disorders. In: Bradley W, Daroff R, Fenichel G, eds. Neurology in Clinical Practice. The Neurological Disorders. Boston: Butterworth-Heinemann, 1991: 1563-1601.
citation: Adams P, Falek A, Arnold J. Huntington disease in Georgia: age at onset. Am J Hum Genet. 1988 Nov;43(5):695-704.
citation: Conneally PM. Huntington disease: genetics and epidemiology. Am J Hum Genet. 1984 May;36(3):506-26.
citation: Harper PS. The epidemiology of Huntington's disease. Hum Genet. 1992 Jun;89(4):365-76. doi: 10.1007/BF00194305.
citation: Tanner CM, Goldman SM. Epidemiology of movement disorders. Curr Opin Neurol. 1994 Aug;7(4):340-5. doi: 10.1097/00019052-199408000-00011. No abstract available.
citation: Young AB, Shoulson I, Penney JB, Starosta-Rubinstein S, Gomez F, Travers H, Ramos-Arroyo MA, Snodgrass SR, Bonilla E, Moreno H, et al. Huntington's disease in Venezuela: neurologic features and functional decline. Neurology. 1986 Feb;36(2):244-9. doi: 10.1212/wnl.36.2.244.
citation: Bruyn G. Huntington's chorea: Historical clinical and laboratory synopsis. In: Vinken P, Bruyn G, eds. Handbook of Clinical Neurology. Amsterdam, 1968: 298-378.
citation: Leigh RJ, Newman SA, Folstein SE, Lasker AG, Jensen BA. Abnormal ocular motor control in Huntington's disease. Neurology. 1983 Oct;33(10):1268-75. doi: 10.1212/wnl.33.10.1268.
citation: Caine ED, Hunt RD, Weingartner H, Ebert MH. Huntington's dementia. Clinical and neuropsychological features. Arch Gen Psychiatry. 1978 Mar;35(3):377-84. doi: 10.1001/archpsyc.1978.01770270127013.
citation: Bamford KA, Caine ED, Kido DK, Plassche WM, Shoulson I. Clinical-pathologic correlation in Huntington's disease: a neuropsychological and computed tomography study. Neurology. 1989 Jun;39(6):796-801. doi: 10.1212/wnl.39.6.796.
citation: Sorensen SA, Fenger K. Causes of death in patients with Huntington's disease and in unaffected first degree relatives. J Med Genet. 1992 Dec;29(12):911-4. doi: 10.1136/jmg.29.12.911.
citation: Oliver JE. Huntington's chorea in Northamptonshire. Br J Psychiatry. 1970 Mar;116(532):241-53. doi: 10.1192/bjp.116.532.241. No abstract available.
citation: Greenamyre J, Shoulson I. Huntington's Disease. In: Calne D, ed. Neurodegenerative Diseases. Philadelphia: WB Saunders, 1994: 685-704.
citation: Shoulson I, Fahn S. Huntington disease: clinical care and evaluation. Neurology. 1979 Jan;29(1):1-3. doi: 10.1212/wnl.29.1.1. No abstract available.
citation: Feigin A, Kieburtz K, Bordwell K, Como P, Steinberg K, Sotack J, Zimmerman C, Hickey C, Orme C, Shoulson I. Functional decline in Huntington's disease. Mov Disord. 1995 Mar;10(2):211-4. doi: 10.1002/mds.870100213.
citation: Myers RH, Sax DS, Koroshetz WJ, Mastromauro C, Cupples LA, Kiely DK, Pettengill FK, Bird ED. Factors associated with slow progression in Huntington's disease. Arch Neurol. 1991 Aug;48(8):800-4. doi: 10.1001/archneur.1991.00530200036015.
citation: Penney JB Jr, Young AB, Shoulson I, Starosta-Rubenstein S, Snodgrass SR, Sanchez-Ramos J, Ramos-Arroyo M, Gomez F, Penchaszadeh G, Alvir J, et al. Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals. Mov Disord. 1990;5(2):93-9. doi: 10.1002/mds.870050202.
citation: Young AB, Penney JB, Starosta-Rubinstein S, Markel DS, Berent S, Giordani B, Ehrenkaufer R, Jewett D, Hichwa R. PET scan investigations of Huntington's disease: cerebral metabolic correlates of neurological features and functional decline. Ann Neurol. 1986 Sep;20(3):296-303. doi: 10.1002/ana.410200305.
citation: Kido D, Shoulson I, Manzione J, Harnish P. Measurement of caudate nucleus and putamen atrophy in patients with Huntington's disease. Neuroradiology 1991;33:604-606.
citation: Mazziotta JC. Huntington's disease: studies with structural imaging techniques and positron emission tomography. Semin Neurol. 1989 Dec;9(4):360-9. doi: 10.1055/s-2008-1041346. No abstract available.
citation: Beal MF, Ferrante RJ. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat Rev Neurosci. 2004 May;5(5):373-84. doi: 10.1038/nrn1386. No abstract available.
citation: A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971-83. doi: 10.1016/0092-8674(93)90585-e.
citation: Tabrizi SJ, Workman J, Hart PE, Mangiarini L, Mahal A, Bates G, Cooper JM, Schapira AH. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann Neurol. 2000 Jan;47(1):80-6. doi: 10.1002/1531-8249(200001)47:13.3.co;2-b.
citation: Cha JH. Transcriptional dysregulation in Huntington's disease. Trends Neurosci. 2000 Sep;23(9):387-92. doi: 10.1016/s0166-2236(00)01609-x.
citation: Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ, Chung WM, Frey AS, Menon AS, Li XJ, Stieg PE, Yuan J, Penney JB, Young AB, Cha JH, Friedlander RM. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature. 1999 May 20;399(6733):263-7. doi: 10.1038/20446.
citation: Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000 Jul;6(7):797-801. doi: 10.1038/77528.
citation: Beal MF, Hyman BT, Koroshetz W. Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci. 1993 Apr;16(4):125-31. doi: 10.1016/0166-2236(93)90117-5.
citation: Wellington CL, Ellerby LM, Hackam AS, Margolis RL, Trifiro MA, Singaraja R, McCutcheon K, Salvesen GS, Propp SS, Bromm M, Rowland KJ, Zhang T, Rasper D, Roy S, Thornberry N, Pinsky L, Kakizuka A, Ross CA, Nicholson DW, Bredesen DE, Hayden MR. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem. 1998 Apr 10;273(15):9158-67. doi: 10.1074/jbc.273.15.9158.
citation: Brouillet E, Hantraye P, Ferrante RJ, Dolan R, Leroy-Willig A, Kowall NW, Beal MF. Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7105-9. doi: 10.1073/pnas.92.15.7105.
citation: Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH. Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol. 1996 Mar;39(3):385-9. doi: 10.1002/ana.410390317.
citation: Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol. 1997 Feb;41(2):160-5. doi: 10.1002/ana.410410206.
citation: Sawa A, Wiegand GW, Cooper J, Margolis RL, Sharp AH, Lawler JF Jr, Greenamyre JT, Snyder SH, Ross CA. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat Med. 1999 Oct;5(10):1194-8. doi: 10.1038/13518.
citation: Jenkins BG, Koroshetz WJ, Beal MF, Rosen BR. Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology. 1993 Dec;43(12):2689-95. doi: 10.1212/wnl.43.12.2689.
citation: Lodi R, Schapira AH, Manners D, Styles P, Wood NW, Taylor DJ, Warner TT. Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann Neurol. 2000 Jul;48(1):72-6.
citation: Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat Neurosci. 2002 Aug;5(8):731-6. doi: 10.1038/nn884.
citation: Gines S, Seong IS, Fossale E, Ivanova E, Trettel F, Gusella JF, Wheeler VC, Persichetti F, MacDonald ME. Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. Hum Mol Genet. 2003 Mar 1;12(5):497-508. doi: 10.1093/hmg/ddg046.
citation: Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MM, Bird ED, Beal MF. Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann Neurol. 1997 May;41(5):646-53. doi: 10.1002/ana.410410514.
citation: Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci. 2000 Jun 15;20(12):4389-97. doi: 10.1523/JNEUROSCI.20-12-04389.2000.
citation: Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM, Beal MF. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J Neurosci. 2002 Mar 1;22(5):1592-9. doi: 10.1523/JNEUROSCI.22-05-01592.2002.
citation: Dedeoglu A, Kubilus JK, Yang L, Ferrante KL, Hersch SM, Beal MF, Ferrante RJ. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem. 2003 Jun;85(6):1359-67. doi: 10.1046/j.1471-4159.2003.01706.x.
citation: Schilling G, Coonfield ML, Ross CA, Borchelt DR. Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington's disease transgenic mouse model. Neurosci Lett. 2001 Nov 27;315(3):149-53. doi: 10.1016/s0304-3940(01)02326-6.
citation: Matthews RT, Yang L, Browne S, Baik M, Beal MF. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8892-7. doi: 10.1073/pnas.95.15.8892.
citation: Beal MF, Henshaw DR, Jenkins BG, Rosen BR, Schulz JB. Coenzyme Q10 and nicotinamide block striatal lesions produced by the mitochondrial toxin malonate. Ann Neurol. 1994 Dec;36(6):882-8. doi: 10.1002/ana.410360613.
citation: Pepping J. Coenzyme Q10. Am J Health Syst Pharm. 1999 Mar 15;56(6):519-21. doi: 10.1093/ajhp/56.6.519. No abstract available.
citation: Musumeci O, Naini A, Slonim AE, Skavin N, Hadjigeorgiou GL, Krawiecki N, Weissman BM, Tsao CY, Mendell JR, Shanske S, De Vivo DC, Hirano M, DiMauro S. Familial cerebellar ataxia with muscle coenzyme Q10 deficiency. Neurology. 2001 Apr 10;56(7):849-55. doi: 10.1212/wnl.56.7.849.
citation: Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta. 1995 May 24;1271(1):195-204. doi: 10.1016/0925-4439(95)00028-3.
citation: Yamagami T, Okishio T, Toyama S, Kishi T. Correlation of serum coenzyme Q10 level and leukocute complex II activity in nformal and cardiovascular patients. In: Folkers K, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q: Elsevier Science Publishers, 1981: 79-89.
citation: Soderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human brain during aging. J Neurochem. 1990 Feb;54(2):415-23. doi: 10.1111/j.1471-4159.1990.tb01889.x.
citation: Peyser CE, Folstein M, Chase GA, Starkstein S, Brandt J, Cockrell JR, Bylsma F, Coyle JT, McHugh PR, Folstein SE. Trial of d-alpha-tocopherol in Huntington's disease. Am J Psychiatry. 1995 Dec;152(12):1771-5. doi: 10.1176/ajp.152.12.1771.
citation: Ranen NG, Peyser CE, Coyle JT, Bylsma FW, Sherr M, Day L, Folstein MF, Brandt J, Ross CA, Folstein SE. A controlled trial of idebenone in Huntington's disease. Mov Disord. 1996 Sep;11(5):549-54. doi: 10.1002/mds.870110510.
citation: Kremer B, Clark CM, Almqvist EW, Raymond LA, Graf P, Jacova C, Mezei M, Hardy MA, Snow B, Martin W, Hayden MR. Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial. Neurology. 1999 Sep 22;53(5):1000-11. doi: 10.1212/wnl.53.5.1000.
citation: Puri BK, Leavitt BR, Hayden MR, Ross CA, Rosenblatt A, Greenamyre JT, Hersch S, Vaddadi KS, Sword A, Horrobin DF, Manku M, Murck H. Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial. Neurology. 2005 Jul 26;65(2):286-92. doi: 10.1212/01.wnl.0000169025.09670.6d.
citation: Dubois B, Brand M, Garcia de Yebenes J, et al. European-Huntington's-disease-Initiative (EHDI)-Trial: Objectives, design, and description of the study population at the end of inclusion. Mov Dis 2002;17:S319.
citation: Bogentoft C, Edelund P, Olsson B, Widlund L, Westensen K. Biopharmaceutical aspects of intraveneous and oral administration of coenzyme Q10. In: Folkers K, Littarru G, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q.: Elsevier Science Publishers, 1991: 215-224.
citation: Lucker P, Wetselsberg N, Hennings G, Rehn D. Pharmacokinetics of coenzyme ubidecarenone in healthy volunteers. In: Folkers K, Littarru G, Yamagami T, eds. Biomedical and clinical aspects of coenzyme Q: Elsevier Science Publishers, 1984: 143-151.
citation: Mohr D, Bowry VW, Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochim Biophys Acta. 1992 Jun 26;1126(3):247-54. doi: 10.1016/0005-2760(92)90237-p.
citation: Micromedex. Ubidecarenone drug monograph. Engelwood 1995 May; Update 1998 Mar.
citation: Zhang Y, Aberg F, Appelkvist EL, Dallner G, Ernster L. Uptake of dietary coenzyme Q supplement is limited in rats. J Nutr. 1995 Mar;125(3):446-53. doi: 10.1093/jn/125.3.446.
citation: Weber C. Dietary intake and absorption of coenzyme Q. In: Kagan V, Quinn P, eds. Coenzyme Q: Molecular Mechanisms in Health and Disease. Boca Raton: CRC Press, 2001:209-215.
citation: Rundek T, Naini A, Sacco R, Coates K, DiMauro S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol. 2004 Jun;61(6):889-92. doi: 10.1001/archneur.61.6.889.
citation: Saito Y, Kubo H, Bujo H, Yamamoto Y. The changes in plasma coenzyme Q10 level during the statin therapy for hypercholesterolemic patients. In: Second Conference of the International Coenzyme Q10 Association.; 2000, 2000: 59.
citation: De Pinieux G, Chariot P, Ammi-Said M, Louarn F, Lejonc JL, Astier A, Jacotot B, Gherardi R. Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol. 1996 Sep;42(3):333-7. doi: 10.1046/j.1365-2125.1996.04178.x.
citation: Watts GF, Castelluccio C, Rice-Evans C, Taub NA, Baum H, Quinn PJ. Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin. J Clin Pathol. 1993 Nov;46(11):1055-7. doi: 10.1136/jcp.46.11.1055.
citation: Laaksonen R, Jokelainen K, Laakso J, Sahi T, Harkonen M, Tikkanen MJ, Himberg JJ. The effect of simvastatin treatment on natural antioxidants in low-density lipoproteins and high-energy phosphates and ubiquinone in skeletal muscle. Am J Cardiol. 1996 Apr 15;77(10):851-4. doi: 10.1016/S0002-9149(97)89180-1.
citation: Huntington Study Group. Minocycline safety and tolerability in Huntington disease. Neurology. 2004 Aug 10;63(3):547-9. doi: 10.1212/01.wnl.0000133403.30559.ff.
citation: Langsjoen H, Langsjoen P, Langsjoen P, Willis R, Folkers K. Usefulness of coenzyme Q10 in clinical cardiology: a long-term study. Mol Aspects Med. 1994;15 Suppl:s165-75. doi: 10.1016/0098-2997(94)90026-4.
citation: Ogasahara S, Engel AG, Frens D, Mack D. Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2379-82. doi: 10.1073/pnas.86.7.2379.
citation: Di Giovanni S, Mirabella M, Spinazzola A, Crociani P, Silvestri G, Broccolini A, Tonali P, Di Mauro S, Servidei S. Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology. 2001 Aug 14;57(3):515-8. doi: 10.1212/wnl.57.3.515.
citation: Lodi R, Hart PE, Rajagopalan B, Taylor DJ, Crilley JG, Bradley JL, Blamire AM, Manners D, Styles P, Schapira AH, Cooper JM. Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia. Ann Neurol. 2001 May;49(5):590-6.
citation: Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50. doi: 10.1001/archneur.59.10.1541.
citation: Shults CW, Flint Beal M, Song D, Fontaine D. Pilot trial of high dosages of coenzyme Q10 in patients with Parkinson's disease. Exp Neurol. 2004 Aug;188(2):491-4. doi: 10.1016/j.expneurol.2004.05.003.
citation: Greenberg S, Frishman WH. Co-enzyme Q10: a new drug for cardiovascular disease. J Clin Pharmacol. 1990 Jul;30(7):596-608. doi: 10.1002/j.1552-4604.1990.tb01862.x.
citation: McGarry A, Auinger P, Kieburtz KD, Bredlau AL, Hersch SM, Rosas HD. Suicidality Risk Factors Across the CARE-HD, 2CARE, and CREST-E Clinical Trials in Huntington Disease. Neurol Clin Pract. 2022 Apr;12(2):131-138. doi: 10.1212/CPJ.0000000000001161.
citation: McGarry A, McDermott MP, Kieburtz K, Fung WLA, McCusker E, Peng J, de Blieck EA, Cudkowicz M; Huntington Study Group 2CARE Investigators and Coordinators. Risk factors for suicidality in Huntington disease: An analysis of the 2CARE clinical trial. Neurology. 2019 Apr 2;92(14):e1643-e1651. doi: 10.1212/WNL.0000000000007244. Epub 2019 Mar 8.
citation: McGarry A, McDermott M, Kieburtz K, de Blieck EA, Beal F, Marder K, Ross C, Shoulson I, Gilbert P, Mallonee WM, Guttman M, Wojcieszek J, Kumar R, LeDoux MS, Jenkins M, Rosas HD, Nance M, Biglan K, Como P, Dubinsky RM, Shannon KM, O'Suilleabhain P, Chou K, Walker F, Martin W, Wheelock VL, McCusker E, Jankovic J, Singer C, Sanchez-Ramos J, Scott B, Suchowersky O, Factor SA, Higgins DS Jr, Molho E, Revilla F, Caviness JN, Friedman JH, Perlmutter JS, Feigin A, Anderson K, Rodriguez R, McFarland NR, Margolis RL, Farbman ES, Raymond LA, Suski V, Kostyk S, Colcher A, Seeberger L, Epping E, Esmail S, Diaz N, Fung WL, Diamond A, Frank S, Hanna P, Hermanowicz N, Dure LS, Cudkowicz M; Huntington Study Group 2CARE Investigators and Coordinators. A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease. Neurology. 2017 Jan 10;88(2):152-159. doi: 10.1212/WNL.0000000000003478. Epub 2016 Dec 2.