Effects of Coenzyme Q10 (CoQ) in Parkinson Disease

Parkinson Disease Clinical Trial

— QE3  

Official title:

Effects of Coenzyme Q10 in Parkinson Disease - Phase III

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00740714
• Other study ID #: U01NS050324
• Secondary ID: U01NS050573
• Status: Terminated
• Phase: Phase 3
• First received: August 22, 2008
• Last updated: December 24, 2012
• Start date: December 2008
• Est. completion date: August 2011

Study information

• Verified date: December 2012
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and effectiveness of high dosages of Coenzyme Q10 in slowing clinical decline in people who have early Parkinson disease.

Description:

Parkinson disease (PD) is a progressive neurodegenerative disease that affects more than 1,000,000 Americans. Currently there is no proven therapy to reduce the rate of progression of PD. In a previous phase II clinical trial, investigators demonstrated that Coenzyme Q10 (CoQ) at dosages of 300, 600, and 1200 mg/day was safe and well-tolerated in individuals with early, untreated PD. The findings also suggested that CoQ may slow the progressive impairment of PD as measured by the Unified Parkinson Disease Rating Scale (UPDRS).

In this study, researchers will conduct a randomized, placebo-controlled, phase III trial of CoQ to confirm and extend the results of the earlier phase II study. The primary objective of this trial is to compare the effect of two dosages of CoQ (1200 and 2400 mg/day) and placebo on the total UPDRS score in people with early PD. The study also will evaluate independent function, cognition, and quality of life. Plasma CoQ levels will be measured at months 1, 8 and 16 and correlated with changes in UPDRS scores.

Participants will be randomly assigned to receive a placebo (an inactive substance), 1200 mg/d CoQ, or 2400 mg/d CoQ. They will be evaluated at screening, baseline, and during visits at months 1, 4, 8, 12, and 16. Information gained from this trial could lead to changes in management of people with early PD.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 600
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• Presence of all 3 of the cardinal features of Parkinson disease (resting tremor, bradykinesia and rigidity). The clinical signs must be asymmetric.

• The diagnosis of Parkinson disease within 5 years prior to the Screening Visit.

• Age 30 or older.

• Female subjects must not be of childbearing potential or must use an approved form of contraception for the duration of the trial.

Exclusion Criteria:

• Use of any Parkinson disease medication within 60 days prior to the Baseline Visit.

• Duration of previous use of symptomatic medication for Parkinson disease cannot exceed 90 days such as levodopa, dopaminergic agonists (including ropinirole, pramipexole, pergolide, cabergoline, and the rotigotine transdermal system), selegiline, rasagiline, amantadine, and anticholinergic agents.

• Parkinsonism due to drugs including neuroleptics, alphamethyldopa, reserpine, metoclopramide, valproic acid.

• Use of antioxidants (such as selegiline, rasagiline, vitamins E and C), additional supplemental vitamins or minerals, regular use of neuroleptics, chloramphenicol, valproic acid, warfarin.

• Other parkinsonian disorders.

• Modified Hoehn and Yahr score of 3 or greater at Screening Visit or Baseline Visit.

• UPDRS tremor score of 3 or greater at Screening Visit or Baseline Visit.

• Mini-Mental State Examination (MMSE) score of 25 or less.

• History of stroke.

• Disability sufficient to require treatment with dopaminergic medication or anticipated need for dopaminergic medication within next 3 months.

• Other serious illness, including psychiatric illness.

• Patients with active cardiovascular, peripheral vascular or cerebrovascular disease within the past year.

• Clinically serious abnormalities in the Screening Visit laboratory studies or electrocardiogram.

• Use of methylphenidate, cinnarizine, reserpine, amphetamine or a MAO-A inhibitor within 6 months prior to the Baseline Visit.

• Unstable dose of CNS active therapies.

• Use of appetite suppressants within 60 days prior to the Baseline Visit.

• History of active epilepsy within the last 5 years.

• Revised Hamilton Rating Scale for Depression of 11 or greater.

• Participation in other drug studies or use of other investigational drugs within 30 days prior to Screening Visit.

• History of electroconvulsive therapy.

• History of any brain surgery for Parkinson disease.

• History of structural brain disease such as prior trauma causing damage detected on a CT scan or MRI, hydrocephalus, or prior brain neoplasms.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Coenzyme Q10 with vitamin E
2400 mg dose - eight 300 mg Coenzyme Q10 chewable wafers taken orally four times a day; 1200 mg dose - four 300 mg Coenzyme Q10 and four placebo chewable wafers taken orally four times a day.
• placebo with vitamin E
placebo or an inactive substance (with vitamin E 1200 IU/day); Placebo - eight chewable wafers taken orally four times a day.

Locations

Country	Name	City	State
Canada	Un of Calgary Movement Disorders Program, Dept of Clin Neurosciences Area 3 Neurology, 3350 Hospital Dr NW Health Sciences Centre	Calgary	Alberta
Canada	University of Alberta Glenrose Rehab Hosp, Rm 0601 Glen East, 10230 - 111 Avenue	Edmonton	Alberta
Canada	London Health Sciences Centre, University Campus Room 10N29, 339 Windermere Road	London	Ontario
Canada	CHUM-HOPITAL NOTRE DAME, 1560 rue SHERBROOKE est ROOM GR 1185, PAVILLON DECHAMPS etage rez-de-chaussee	Montreal	Quebec
Canada	The Ottawa Hospital-Civic Campus, 1053 Carling Avenue C2 Room 2210	Ottawa	Ontario
Canada	Quebec Memory and Motor Skills Dis Clinic, Price Building 3Rd Floor, 65 Sainte-Anne Street	Quebec
Canada	Royal University Hospital, 103 Hospital Drive, Room 1663	Saskatoon	Saskatchewan
Canada	University of Sherbrooke, 3001 12E Avenue Nord	Sherbrooke	Quebec
Canada	Toronto Western Hospital, Univ Health Network, 399 Bathurst Street Mc 7-402, Movement Disorders Centre	Toronto	Ontario
United States	Albany Medical College, Parkinson'S Disease & Movement Disorders Ctr, 47 New Scottland Avenue	Albany	New York
United States	Emory University School of Medicine, Wesley Woods Health Center, 1841 Clifton Road NE Room 328	Atlanta	Georgia
United States	Movement Disorders Program, Department of Neurology, Medical College of Georgia	Augusta	Georgia
United States	Department of Neurology/Mail Stop B185, 12631 East 17Th Avenue Room 5209, Academic Office 1 Po Box 6511	Aurora	Colorado
United States	Johns Hopkins, 601 North Caroline Street, Suite 5064	Baltimore	Maryland
United States	University of Maryland School of Medicine, 22 South Greene Street, N4 W49-B	Baltimore	Maryland
United States	University of Alabama, Birmingham, 350 Sparks Center, 1720 7Th Avenue South	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Shapiro 809D	Boston	Massachusetts
United States	Boston University Medical Center, Department of Neurology, 715 Albany Street C329	Boston	Massachusetts
United States	JACOBI MEDICAL CENTER, 1400 Pelham Pkwy S	Bronx	New York
United States	Suny Downstate Medical Center , 450 Clarkson Avenue , Box 1213	Brooklyn	New York
United States	University of Vermont , Department of Neurology Given Building C-219 , 89 Beaumont Avenue	Burlington	Vermont
United States	Medical University of South Carolina, Charleston Memorial Hospital, 326 Calhoun Street Suite 308	Charleston	South Carolina
United States	Northwestern University, 710 North Lake Shore Drive	Chicago	Illinois
United States	Rush University Medical Center Department of Neurological Sciences, 1725 West Harrison Suite 755	Chicago	Illinois
United States	University of Chicago, 5841 South Maryland Avenue, Mc2030	Chicago	Illinois
United States	University Neurology Inc., 222 Piedmont Avenue, Suite 3200	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation, 9500 Euclid Avenue S-31	Cleveland	Ohio
United States	Ohio State University Medical Center, 1581 Dodd Drive, 371 McCampbell Hall	Columbus	Ohio
United States	Duke University Medical Center, Duke Health Center At Morreene Road, 932 Morreene Road Room 213	Durham	North Carolina
United States	Parkinson & Movement Dis Center If Maryland, 8180 Lark Brown Road, Suite 101	Elkridge	Maryland
United States	The Parkinson'S & Movement Disorder Institute, 9940 Talbert Avenue, Suite 204	Fountain Valley	California
United States	University of Florida, McKnight Brain Institute Po Box 100236, 100 S Newell Drive L3-100	Gainsville	Florida
United States	Penn State Milton S Hershey Med Center, Department of Neurology Mc H109 Room 2846, 500 University Drive Po Box 850	Hershey	Pennsylvania
United States	Baylor College of Medicine - Parkinson'S, Disease Center and Movement Disorders Clinic, 65501 Fannin St, Suite 1801	Houston	Texas
United States	Indiana University School of Medicine, Outpatient Clinical Research Facility, 535 Barnhill Drive Room #150	Indianapolis	Indiana
United States	University of Iowa Hospitals, 2133 Rcp Department of Neurology, 200 Hawkins Drive	Iowa City	Iowa
United States	University of California Irvine, 100 Irvine Hall	Irvine	California
United States	The University of Kansas Medical Center, Department of Neurology Ms #2012, 3599 Rainbow Boulevard	Kansas City	Kansas
United States	Booth Gardner Parkinson'S Care Center, 13030 121St Way North East Suite 203	Kirkland	Washington
United States	University of California San Diego, Alzheimer'S Disease Research Center, 9500 Gilman Drive	La Jolla	California
United States	Colorado Neurological Institute, 701 East Hampden Avenue, Suite 510	Littleton	Colorado
United States	UCLA Medical Center, 710 Westwood Plaza, A-253	Los Angeles	California
United States	University of Louisville, Movement Disorder Clinic, Frazier Rehab, 220 Abraham Flexner, Suite 606	Louisville	Kentucky
United States	Northshore-Lij Health System, the Feinstein Institute Fpr Medical Research, 350 Community Drive Room 100	Manhasset	New York
United States	Semmes Murphey Clinic, 1211 Union Avenue, Suite 200	Memphis	Tennessee
United States	University of Miami, 1501 North West 9Th Avenue Second Floor, Department of Neurology D4-5	Miami	Florida
United States	Medical College of Wisconsin, Department of Neurology, 9200 West Wisconsin Avenue	Milwaukee	Wisconsin
United States	University of Minnesota, 420 Delaware Street SE, Mmc 295	Minneapolis	Minnesota
United States	The Institute For Neurodegenerative Disorders, 60 Temple Street, Suite 8B	New Haven	Connecticut
United States	Ochsner Clinic Foundation, 1514 Jefferson Highway, Dept of Neurology 7Th Floor	New Orleans	Louisiana
United States	Beth Israel Medical Center, 10 Union Square East, Suite 5Hh2	New York	New York
United States	Beth Israel Medical Center, Phillips Ambulatory Care Center, 10 Union Square East Room 5Ho1	New York	New York
United States	Columbia University, 710 West 168Th Street, 3Rd Floor	New York	New York
United States	Parkinson`S Dis & Movement Disorders Inst, 428 East 72Nd Street, Suite 400	New York	New York
United States	Weill Medical College of Cornell	New York	New York
United States	University of Pennsylvania, Pennsylvania Hospital Department of Neurology, 330 South 9Th Street	Philadelphia	Pennsylvania
United States	Barrow Neurological Clinics At St Joseph`S Hospital & Medical Center, 500 West Thomas Road Suite 720	Phoenix	Arizona
United States	Oregon Health & Science University, Dept of Neurology, 3181 SW Sam Jackson Park Road Op-32	Portland	Oregon
United States	University of Rochester Department of Neurology, 919 Westfall Road Building C Suite 220	Rochester	New York
United States	UC Davis Dept of Neurology, 4860 Y Street, Suite 3700	Sacramento	California
United States	Mayo Clinic Arizona, 13400 East Shea Boulevard, Desk 34 3B	Scottsdale	Arizona
United States	Lsuhsc Shreveport, Department of Neurology, 1501 Kings Highway Room 3-436	Shreveport	Louisiana
United States	Washington University School of Medicine, 660 South Euclid, Box 8111	St Louis	Missouri
United States	Sunhealth Research Institute, 10515 West Santa Fe Drive	Sun City	Arizona
United States	The Parkinson's Institute, 675 ALMANOR AVENUE	Sunnyvale	California
United States	University of South Florida, 4 Columbia Drive, Suite 410	Tampa	Florida
United States	University of Toledo , 3000 Arlington Avenue , Mail Stop 1195	Toledo	Ohio
United States	Neurohealth Parkinson'S Disease, Movement Disorder Center, 227 Centerville Road	Warwick	Rhode Island

Sponsors (3)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute of Neurological Disorders and Stroke (NINDS), University of Rochester

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (18)

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. — View Citation

Beal MF, Matthews RT, Tieleman A, Shults CW. Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res. 1998 Feb 2;783(1):109-14. — View Citation

Beal MF. Coenzyme Q10 as a possible treatment for neurodegenerative diseases. Free Radic Res. 2002 Apr;36(4):455-60. Review. — View Citation

Beal MF. Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci. 2000 Jul;23(7):298-304. Review. — View Citation

Blatt DH, Pryor WA. High-dosage vitamin E supplementation and all-cause mortality. Ann Intern Med. 2005 Jul 19;143(2):150-1; author reply 156-8. — View Citation

Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):56-65. — View Citation

McDonald SR, Sohal RS, Forster MJ. Concurrent administration of coenzyme Q10 and alpha-tocopherol improves learning in aged mice. Free Radic Biol Med. 2005 Mar 15;38(6):729-36. — View Citation

Meydani SN, Lau J, Dallal GE, Meydani M. High-dosage vitamin E supplementation and all-cause mortality. Ann Intern Med. 2005 Jul 19;143(2):153; author reply 156-8. — View Citation

Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. — View Citation

NINDS NET-PD Investigators. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology. 2007 Jan 2;68(1):20-8. — View Citation

Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993 Jan 21;328(3):176-83. — View Citation

Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy DD, Dawson TM, Marler JR. Neuroprotective agents for clinical trials in Parkinson's disease: a systematic assessment. Neurology. 2003 Apr 22;60(8):1234-40. Review. — View Citation

Shoulson I, Oakes D, Fahn S, Lang A, Langston JW, LeWitt P, Olanow CW, Penney JB, Tanner C, Kieburtz K, Rudolph A; Parkinson Study Group. Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson's disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial. Ann Neurol. 2002 May;51(5):604-12. — View Citation

Shults CW, Beal MF, Fontaine D, Nakano K, Haas RH. Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients. Neurology. 1998 Mar;50(3):793-5. — View 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. — View Citation

Shults CW, Haas RH, Passov D, Beal MF. Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol. 1997 Aug;42(2):261-4. — View 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. — View Citation

Shults CW. Coenzyme Q10 in neurodegenerative diseases. Curr Med Chem. 2003 Oct;10(19):1917-21. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Unified Parkinson's Disease Rating Scale (UPDRS) (Total Score (Sum of Parts I, II and III Ranges From 0 to 176))	Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline visit and month 16 or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first. The UPDRS score has three components, each consisting of questions answered on a 0-4 point scale. Part I assesses mentation, behavior and mood; Part II assesses activities of daily living in the week prior to the designated visit; and Part III assesses motor abilities at the time of the visit. A total of 31 items are included in Parts I, II and III. Each item will receive a score ranging from 0 to 4 where 0 represents the absence of impairment and 4 represents the highest degree of impairment. Total score ranges from 0-176.	Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first	No
Secondary	Change in Modified Schwab & England Independence Scale From Baseline to 16 Months	This scale measures activities of daily living. This is an investigator and subject assessment of the subject's level of independence at all scheduled visits. The subject is scored on a percentage scale reflective of his/her ability to perform acts of daily living in relation to pre-Parkinson disease ability. Scores range in increments of 10%: 100% for normal (subject is completely independent; essentially normal) to 0% (vegetative functions such as swallowing, bladder and bowel functions are not functioning; bedridden).	Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first	No
Secondary	Change in Modified Rankin Scale From Baseline to 16 Months	The Modified Rankin Scale is a global functional health index with a strong accent on physical disability. Subjects are scored on a scale of 0 (no symptoms at all) to 5 (severe disability: bedridden incontinent, and requiring constant nursing care and attention.	Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first	No
Secondary	Change in PD Quality of Life Scale From Baseline to 16 Months	The subject will complete a questionnaire that will evaluate how Parkinson disease has affected their health and overall quality of life at each visit. The total quality of life scale measures a total of 33 aspects of quality of life. Each aspect is rated on scale of 0 (best outcome) to 4 (worst outcome). Total score range is 0-132. A higher score or increased score compared to a previous visit indicates a lowered quality of life.	Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first	No
Secondary	Change in Symbol Digit Modalities Test From Baseline to 16 Months	The Symbol Digit Modalities Test screens cognitive impairment by using a simple substitution tasks that individuals with normal functioning can easily perform. The test score range is from 0(worst outcome) to 110 (best outcome).	Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first	No
Secondary	Change in Hoehn & Yahr Score From Baseline to 16 Months	The Modified Hoehn and Yahr Scale is an 8-level Parkinson disease staging instrument. The investigator will assess disease stage at each level. The disease stages range from the best outcome of 0 (no signs of disease) to the worst outcome of 5 (wheelchair bound or bedridden unless aided).	Baseline to 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first	No
Secondary	CoQ10 Levels in Plasma	Based on samples analyzed to date	Baseline, 1, 8 and 16 months or the time of sufficient disability to require dopaminergic therapy or study closure, whichever occurs first	Yes
Secondary	Adverse Experiences: Back Pain	Number of participants with back pain	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Constipation	Number of participants with constipation	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Insomnia	Number of participants with insomnia	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Anxiety	Number of participants with anxiety	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Tremor	Number of participants with tremor	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Nasopharyngitis	Number of participants with nasopharyngitis	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Diarrhoea	Number of participants with diarrhoea	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Headache	Number of participants with headache	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Urinary Tract Infection	Number of patients with urinary tract infections	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Nausea	Number of participants with nausea	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Hypertension	Number of participants with hypertension	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Depression	Number of participants with depression	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Constipation: Moderate/Severe	Number of participants with moderate/severe constipation	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Anxiety: Moderate/Severe	Number of participants with moderate/severe anxiety	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Back Pain: Moderate/Severe	Number of participants with moderate/severe back pain	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes
Secondary	Adverse Experiences: Insomnia: Moderate/Severe	Number of participants with moderate/severe insomnia	Over 16 months (Screening, Baseline, 1, 4, 8, 12 and 16 month visits)	Yes