Huntington's DiseasePhase 3CREST-ENCT00712426
Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
A Phase 3 study testing Creatine Monohydrate in people with Huntington's Disease, run by Massachusetts General Hospital at 47 sites in 4 countries.
Trial summary
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.Creatine monohydrate is considered a nutritional supplement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Huntington's Disease
- What is being tested?
- Creatine Monohydrate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 553 participants
- Where
- 47 sitesin 4 countries
- Study dates
- Sep 2009to Jan 2015
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ages 18 or older.
- Clinical features of HD AND confirmatory family history of HD; OR Clinical features of HD AND CAG repeat expansion greater or equal to 36.
- Stage I or II of illness (TFC greater or equal to 7).
- Ambulatory and not requiring skilled nursing care at the time of enrollment.
- Must be capable of providing informed consent and complying with trial procedures.
- Additional inclusion criteria apply.
Who cannot join
- History of known sensitivity or intolerability to creatine monohydrate.
- Exposure to any investigational drug within 30 days of randomization (Baseline visit).
- Use of supplemental creatine at a dose greater than 10 grams within 30 days of randomization (Baseline visit).
- Screening laboratory abnormalities that in the judgment of the investigator would jeopardize safe conduct of study.
- Clinical evidence of unstable medical illness.
- Clinical evidence of unstable psychiatric illness.
- Additional exclusion criteria apply.
Trial locations and contacts
47 sites in 4 countries.
47 sites in 4 countries
United States38 sites
Albany Medical College
Albany, New York, 12208
University of Michigan
Ann Arbor, Michigan, 48109
Emory University School of Medicine
Atlanta, Georgia, 30329
Georgia Regents University
Augusta, Georgia, 30329
University of Maryland School of Medicine
Baltimore, Maryland, 21201
University of Alabama
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02129
Cooper University Hospital
Camden, New Jersey, 08103
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Health System
Charlottesville, Virginia, 22908
Rush University Medical Center
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43210
Duke University
Durham, North Carolina, 27705
University of Connecticut
Farmington, Connecticut, 06030
University of Florida (McKnight Brain Institute)
Gainesville, Florida, 32610
Struthers Parkinson's Center
Golden Valley, Minnesota, 55427
Baylor College of Medicine
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 27157
University of Iowa
Iowa City, Iowa, 52242
University of California, Irvine
Irvine, California, 92697
University of Kansas Medical Center
Kansas City, Kansas, 66160
Booth Gardner Parkinson's Care Center (Evergreen Healthcare)
Kirkland, Washington, 98034
University of Louisville
Louisville, Kentucky, 40202
North Shore-LIJ Health System
Manhasset, New York, 11030
University of Tennessee Health Science Center
Memphis, Tennessee, 38163
Columbia University Medical Center
New York, New York, 10032
Nebraska Medical Center
Omaha, Nebraska, 68198
University of Pennsylvania
Philadelphia, Pennsylvania, 19107
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
University of Rochester
Rochester, New York, 14618
University of California Davis
Sacramento, California, 95817
University of Utah
Salt Lake City, Utah, 84108
Washington University School of Medicine
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33612
Hereditary Neurological Disease Center (HNDC)
Wichita, Kansas, 67206
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157
Canada5 sites
University of Alberta Hospital
Edmonton, Alberta, T2N 4Z6
University of Alberta
Edmonton, Alberta, T2N 4Z6
CHUM - Hopital Notre-Dame
Montreal, Quebec, H2L 4M1
University of Quebec Infant-Jesus Hospital (Centre Hospitalier Affilie)
Québec, Quebec, G1J 1Z4
Movement Disorder Clinic Deer Lodge Center
Winnipeg, Manitoba, R3J 2H7
Australia2 sites
Neurodegenerative Disorders Research
Subiaco, Western Australia, 6008
Westmead Hospital
Wentworthville, New South Wales, 2145
New Zealand2 sites
Auckland City Hospital
Auckland, 1142
New Zealand Brain Research Institute
Christchurch, 8011
About this study
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.Creatine monohydrate is considered a nutritional supplement. The purpose of CREST-E is to test whether high-dose creatine can slow the progressive functional decline that occurs in persons 18 years or older with early clinical features of HD. The long-term safety, tolerability and effectiveness of up to 40 grams daily creatine compared to placebo is studied. A variety of biological processes are assessed for markers of disease activity or progression and creatine effects. Up to 50 active research centers globally will enroll 650 subjects.
- Conditions
- Huntington's Disease
- Being tested
- Creatine Monohydrate, Placebo
- Keywords
- Huntington's disease, Creatine, Mitochondrial Dysfunction, Total Functional Capacity, UHDRS
- Medical subject headings
- Huntington Disease, Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Creatine MonohydrateDrug
Also called HD-02
Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration
PlaceboDrug
Also called Dextrose
Up to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Randomized to receive creatine monohydrate (up to 40 grams daily) Receives: Drug: Creatine Monohydrate |
| B | Placebo comparator | Randomized to receive placebo (up to 40 grams daily) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Total Functional Capacity
Study duration depends on each subject's calendar date of enrollment.
Measured: Minimum 12 months up to 48 months
Secondary outcomes (1)
Clinical symptoms (changes in other UHDRS scores); safety (frequency of adverse events); tolerability (proportion of subjects completing study at assigned dosage level), quality of life, other biological markers.
Measured: Duration of the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2008 (estimated)
- Study startSep 2009
- Primary completionDec 2014
- Study completionJan 2015
Why it stopped: Results of an interim analysis showed that it was unlikely that creatine was effective in slowing loss of function in early symptomatic Huntington's Disease.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Huntington's DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 553 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Rochester, National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Principal investigator, Steven M. Hersch, Massachusetts General Hospital
- Investigators
- Steven M Hersch, MD, PhD, Principal investigator, Massachusetts General HospitalGiovanni Schifitto, MD, Principal investigator, University of Rochester Clinical Trial Coordination CenterDiana Rosas, MD, MS, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00712426
- Sponsor's protocol ID
- 2007P000827
- Other IDs
- U01AT000613
- Acronym
- CREST-E
- Status last verified
- Feb 2016
- First submitted
- 8 Jul 2008
- Last updated
- 11 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kim J, Amante DJ, Moody JP, Edgerly CK, Bordiuk OL, Smith K, Matson SA, Matson WR, Scherzer CR, Rosas HD, Hersch SM, Ferrante RJ. Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease. Biochim Biophys Acta. 2010 Jul-Aug;1802(7-8):673-81. doi: 10.1016/j.bbadis.2010.05.001. Epub 2010 May 9.
PubMed 20460152Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, Como P, Zimmerman C, Lin M, Zhang L, Ulug AM, Beal MF, Matson W, Bogdanov M, Ebbel E, Zaleta A, Kaneko Y, Jenkins B, Hevelone N, Zhang H, Yu H, Schoenfeld D, Ferrante R, Rosas HD. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG. Neurology. 2006 Jan 24;66(2):250-2. doi: 10.1212/01.wnl.0000194318.74946.b6.
PubMed 16434666Ryu H, Rosas HD, Hersch SM, Ferrante RJ. The therapeutic role of creatine in Huntington's disease. Pharmacol Ther. 2005 Nov;108(2):193-207. doi: 10.1016/j.pharmthera.2005.04.008. Epub 2005 Aug 1.
PubMed 16055197Dedeoglu 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.
PubMed 12787055Andreassen OA, Dedeoglu A, Ferrante RJ, Jenkins BG, Ferrante KL, Thomas M, Friedlich A, Browne SE, Schilling G, Borchelt DR, Hersch SM, Ross CA, Beal MF. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol Dis. 2001 Jun;8(3):479-91. doi: 10.1006/nbdi.2001.0406.
PubMed 11447996Ferrante 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.
PubMed 10844007McGarry 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.
PubMed 35747889Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: August 2018. J Huntingtons Dis. 2018;7(3):279-286. doi: 10.3233/JHD-189003.
PubMed 30103342Hersch SM, Schifitto G, Oakes D, Bredlau AL, Meyers CM, Nahin R, Rosas HD; Huntington Study Group CREST-E Investigators and Coordinators. The CREST-E study of creatine for Huntington disease: A randomized controlled trial. Neurology. 2017 Aug 8;89(6):594-601. doi: 10.1212/WNL.0000000000004209. Epub 2017 Jul 12.
PubMed 28701493
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Creatine Safety, Tolerability, & Efficacy in Huntington's Disease (CREST-E)
- ClinicalTrials.gov ID
- NCT00712426
- Acronym / sponsor ID
- CREST-E / 2007P000827
- Conditions
- Huntington's Disease
- Keywords
- Huntington's disease, Creatine, Mitochondrial Dysfunction, Total Functional Capacity, UHDRS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Results of an interim analysis showed that it was unlikely that creatine was effective in slowing loss of function in early symptomatic Huntington's Disease.
- Enrolment
- 553 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- University of Rochester, National Center for Complementary and Integrative Health (NCCIH)
- Study start
- Sep 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 10 Jul 2008 (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.
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.Creatine monohydrate is considered a nutritional supplement. The purpose of CREST-E is to test whether high-dose creatine can slow the progressive functional decline that occurs in persons 18 years or older with early clinical features of HD. The long-term safety, tolerability and effectiveness of up to 40 grams daily creatine compared to placebo is studied. A variety of biological processes are assessed for markers of disease activity or progression and creatine effects. Up to 50 active research centers globally will enroll 650 subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Creatine MonohydrateRandomized to receive creatine monohydrate (up to 40 grams daily) |
| B | Placebo comparator | Drug: PlaceboRandomized to receive placebo (up to 40 grams daily) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female ages 18 or older.
- Clinical features of HD AND confirmatory family history of HD; OR Clinical features of HD AND CAG repeat expansion greater or equal to 36.
- Stage I or II of illness (TFC greater or equal to 7).
- Ambulatory and not requiring skilled nursing care at the time of enrollment.
- Must be capable of providing informed consent and complying with trial procedures.
Key exclusion criteria (7 listed)
- History of known sensitivity or intolerability to creatine monohydrate.
- Exposure to any investigational drug within 30 days of randomization (Baseline visit).
- Use of supplemental creatine at a dose greater than 10 grams within 30 days of randomization (Baseline visit).
- Screening laboratory abnormalities that in the judgment of the investigator would jeopardize safe conduct of study.
- Clinical evidence of unstable medical illness.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Creatine MonohydrateAlso: HD-02Up to 40 grams daily, powder form creatine monohydrate, taken for the trial duration | Drug | A |
| PlaceboAlso: DextroseUp to 40 grams daily, powder form placebo (inactive substance), taken for the trial duration | Drug | B |
Primary outcome
Change in Total Functional Capacity
Time frame: Minimum 12 months up to 48 months
Study duration depends on each subject's calendar date of enrollment.
1 secondary outcome
Clinical symptoms (changes in other UHDRS scores); safety (frequency of adverse events); tolerability (proportion of subjects completing study at assigned dosage level), quality of life, other biological markers.
Time frame: Duration of the trial
Results and safety
The study was stopped early (reason given: Results of an interim analysis showed that it was unlikely that creatine was effective in slowing loss of function in early symptomatic Huntington's Disease.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2016.
- Background: PubMed 20460152Kim J, Amante DJ, Moody JP, Edgerly CK, Bordiuk OL, Smith K, Matson SA, Matson WR, Scherzer CR, Rosas HD, Hersch SM, Ferrante RJ. Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease. Biochim Biophys Acta. 2010 Jul-Aug;1802(7-8):673-81. doi: 10.1016/j.bbadis.2010.05.001. Epub 2010 May 9.
- Background: PubMed 16434666Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, Como P, Zimmerman C, Lin M, Zhang L, Ulug AM, Beal MF, Matson W, Bogdanov M, Ebbel E, Zaleta A, Kaneko Y, Jenkins B, Hevelone N, Zhang H, Yu H, Schoenfeld D, Ferrante R, Rosas HD. Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2'dG. Neurology. 2006 Jan 24;66(2):250-2. doi: 10.1212/01.wnl.0000194318.74946.b6.
- Background: PubMed 16055197Ryu H, Rosas HD, Hersch SM, Ferrante RJ. The therapeutic role of creatine in Huntington's disease. Pharmacol Ther. 2005 Nov;108(2):193-207. doi: 10.1016/j.pharmthera.2005.04.008. Epub 2005 Aug 1.
- Background: PubMed 12787055Dedeoglu 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.
- Background: PubMed 11447996Andreassen OA, Dedeoglu A, Ferrante RJ, Jenkins BG, Ferrante KL, Thomas M, Friedlich A, Browne SE, Schilling G, Borchelt DR, Hersch SM, Ross CA, Beal MF. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol Dis. 2001 Jun;8(3):479-91. doi: 10.1006/nbdi.2001.0406.
- Background: PubMed 10844007Ferrante 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.
- Derived from this study: PubMed 35747889McGarry 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.
- Derived from this study: PubMed 30103342Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: August 2018. J Huntingtons Dis. 2018;7(3):279-286. doi: 10.3233/JHD-189003.
- Derived from this study: PubMed 28701493Hersch SM, Schifitto G, Oakes D, Bredlau AL, Meyers CM, Nahin R, Rosas HD; Huntington Study Group CREST-E Investigators and Coordinators. The CREST-E study of creatine for Huntington disease: A randomized controlled trial. Neurology. 2017 Aug 8;89(6):594-601. doi: 10.1212/WNL.0000000000004209. Epub 2017 Jul 12.
- Huntington Study Group (CREST-E Study)Link provided by the sponsor.
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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.
Steven M Hersch, MD, PhD principal investigator
Massachusetts General Hospital
Giovanni Schifitto, MD principal investigator
University of Rochester Clinical Trial Coordination Center
Diana Rosas, MD, MS principal investigator
Massachusetts General Hospital
47 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Creatine Monohydrate in people with Huntington's Disease, run by Massachusetts General Hospital at 47 sites in 4 countries.
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 7 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: stopped early, as of the sponsor's last update on 11 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in United States, Canada, Australia, New Zealand. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Results of an interim analysis showed that it was unlikely that creatine was effective in slowing loss of function in early symptomatic Huntington's Disease.). Results are not available in the source record.
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.
What does the primary outcome measure?
Change in Total Functional Capacity (time frame: Minimum 12 months up to 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00712426, which also lists 9 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 11 Mar 2016.