Huntington's DiseasePhase 2NCT00212316
Safety and Tolerability Study of Phenylbutyrate in Huntington's Disease (PHEND-HD)
A Phase 2 study testing sodium phenylbutyrate in people with Huntington's Disease, run by University of Rochester at 8 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and clinical impact of 15-grams daily of sodium phenylbutyrate (phenylbutyrate) in Huntington's disease and to lay the groundwork for possible subsequent trials designed to specifically address its ability to slow or halt the progression of the disease. 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?
- sodium phenylbutyrate
- How many people
- 60 participants
- Where
- 8 sitesUnited States
- Study dates
- Aug 2005to Jun 2006
- Phase
- Phase 2
- 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
- Subjects with clinical diagnosis of HD and family history of HD or a CAG repeat expansion greater than or equal to 37
- Subjects in stage I or II of illness (TFC greater than or equal to 7)
- Subjects must be ambulatory and not requiring skilled nursing care
- Age of 18 years or older
- Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) must confirm to the best of their knowledge that they are not pregnant or plan to get pregnant
- Women of childbearing potential must have negative pregnancy test, be non-lactating and use adequate contraception methods, such as oral birth control pills plus a barrier method (i.e. condoms, diaphragm) or IUD during their participation in the study
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- Subjects currently taking psychotropic medications (including antidepressants and neuroleptics) must be on stable dosages for at least 4 weeks prior to baseline visit and should be maintained on constant dosage throughout the study
- Subjects must be capable of providing informed consent and complying with trial procedures
- Subjects must be able to take oral medication, a person willing and able to serve as an informant and provide information about the daily dosing of study medication
Who cannot join
- Exposure to phenylbutyrate, valproic acid, probenecid, known HDAC inhibitors or other transcriptionally active compounds within 3 months (90 days) prior to the baseline visit
- History of known sensitivity or intolerability to phenylbutyrate, sodium butyrate or sodium acetate
- Existence of a known malignancy that might require treatment during the course of this study
- Exposure to any investigational drug within 30 days of the baseline visit
- Subjects with underlying hematologic, hepatic or renal disease; screening white blood cell (WBC) count less than 3,800/mm3, screening creatinine greater than 2.0 or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal
- Clinical evidence of unstable medical illness in the investigator's judgment
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- Clinical illness that requires use of warfarin (Coumadin)
- Unstable psychiatric illness defined as psychosis (hallucinations or delusions) untreated major depression or plan for suicide within 90 days of the baseline visit
- Current or history of substance (alcohol or drug) abuse within 1 year of the baseline visit
- Pregnant women or women who are currently breast-feeding
- History of heart failure or other conditions that might be exacerbated by sodium loading
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Johns Hopkins University
Baltimore, Maryland
University of Alabama
Birmingham, Alabama
Massachusetts General Hospital
Boston, Massachusetts
University of Iowa Hospital and Clinics
Iowa City, Iowa
University of Kansas Medical Center
Kansas City, Kansas
Columbia University
New York, New York
University of Rochester
Rochester, New York
University of California-San Diego
San Diego, California
About this study
Official title: Phenylbutyrate Development for Huntington's Disease (PHEND-HD): A Multi-Center, Double-Blind, Placebo-Controlled Study With Open-Label Follow-Up to Determine the Safety and Tolerability of Phenylbutyrate in Subjects With Huntington's Disease
The purpose of this study is to evaluate the safety, tolerability and clinical impact of 15-grams daily of sodium phenylbutyrate (phenylbutyrate) in Huntington's disease and to lay the groundwork for possible subsequent trials designed to specifically address its ability to slow or halt the progression of the disease.
Read the detailed description
Huntington's disease (HD) is an autosomal dominant disorder resulting in selective loss of neurons in the striatum-an area of the brain that controls movement, balance, and walking-and other areas of the brain. The disease is characterized by progressive motor and cognitive decline. There is no cure or even plausible treatment to offset the fatal course of the disease. Therefore, any treatment that ameliorates the disease would be of enormous importance.
The purpose of this double-blind, placebo-controlled study-with open-label follow-up-is to determine the safety and tolerability of 15-grams daily of oral phenylbutyrate in people with HD. The study will enroll 60 individuals. Eligible participants will be initially randomized to receive either phenylbutyrate or the matching placebo for 4 weeks.
After the placebo-controlled phase, all participants will enter the open-label phase to receive phenylbutyrate for 12 weeks. Participants will be followed for one month off phenylbutyrate.
This combination of a short-term double-blind, placebo-controlled phase followed by a longer open-label phase will favor the primary goals of detecting toxicity and intolerability while facilitating recruitment and maximizing number of subjects on study drug.
- Conditions
- Huntington's Disease
- Being tested
- sodium phenylbutyrate
- Keywords
- Huntington's Disease, phenylbutyrate, HDAC inhibitors, transcription
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sodium phenylbutyrateDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects able to complete treatment (Week 16)
Secondary outcomes (15)
Secondary safety and tolerability outcomes at Weeks 1, 4, 5, 10, 16, & 20 include:
adverse events,
changes in vital signs,
and clinical lab assessments.
Secondary clinical measures at Weeks 4, 10, 16, and 20 include components of the UHDRS:
total motor,
Stroop,
independence,
& total functional capacity.
Secondary biological indicators of treatment affects at Weeks 4, 10, 16, & 20 include:
markers of neuroprotection (e.g. NAA) via MRS,
histone acetylation (levels in WBC; fetal hemoglobin levels in blood),
depletion of glutamine,
gene expression analyses,
and biochemical analyses for pharmacokinetics.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startAug 2005
- Study completionJun 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Huntington's DiseaseStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 60 participants
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- HP Therapeutics Foundation, Massachusetts General Hospital, Columbia University, University of Iowa, University of California, San Diego, University of Kansas, University of Alabama at Birmingham, Johns Hopkins University
- Investigators
- Steven M. Hersch, MD, PhD, Principal investigator, Co-Chair, Huntington Study Group, Massachusetts General HospitalKarl Kieburtz, MD, MPH, Principal investigator, Director, Clinical Trials Coordination Center, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00212316
- Sponsor's protocol ID
- R01NS45242
- Status last verified
- Dec 2007
- First submitted
- 19 Sep 2005
- Last updated
- 15 Aug 2012
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenylbutyrate Development for Huntington's Disease (PHEND-HD): A Multi-Center, Double-Blind, Placebo-Controlled Study With Open-Label Follow-Up to Determine the Safety and Tolerability of Phenylbutyrate in Subjects With Huntington's Disease
- ClinicalTrials.gov ID
- NCT00212316
- Acronym / sponsor ID
- R01NS45242
- Conditions
- Huntington's Disease
- Keywords
- Huntington's Disease, phenylbutyrate, HDAC inhibitors, transcription
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- HP Therapeutics Foundation, Massachusetts General Hospital, Columbia University, University of Iowa, University of California, San Diego, University of Kansas, University of Alabama at Birmingham, Johns Hopkins University
- Study start
- Aug 2005
- Study completion
- Jun 2006 (actual)
- First posted
- 21 Sep 2005 (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.
The purpose of this study is to evaluate the safety, tolerability and clinical impact of 15-grams daily of sodium phenylbutyrate (phenylbutyrate) in Huntington's disease and to lay the groundwork for possible subsequent trials designed to specifically address its ability to slow or halt the progression of the disease.
Detailed description
Huntington's disease (HD) is an autosomal dominant disorder resulting in selective loss of neurons in the striatum-an area of the brain that controls movement, balance, and walking-and other areas of the brain. The disease is characterized by progressive motor and cognitive decline. There is no cure or even plausible treatment to offset the fatal course of the disease. Therefore, any treatment that ameliorates the disease would be of enormous importance.
The purpose of this double-blind, placebo-controlled study-with open-label follow-up-is to determine the safety and tolerability of 15-grams daily of oral phenylbutyrate in people with HD. The study will enroll 60 individuals. Eligible participants will be initially randomized to receive either phenylbutyrate or the matching placebo for 4 weeks.
After the placebo-controlled phase, all participants will enter the open-label phase to receive phenylbutyrate for 12 weeks. Participants will be followed for one month off phenylbutyrate.
This combination of a short-term double-blind, placebo-controlled phase followed by a longer open-label phase will favor the primary goals of detecting toxicity and intolerability while facilitating recruitment and maximizing number of subjects on study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects with clinical diagnosis of HD and family history of HD or a CAG repeat expansion greater than or equal to 37
- Subjects in stage I or II of illness (TFC greater than or equal to 7)
- Subjects must be ambulatory and not requiring skilled nursing care
- Age of 18 years or older
- Women of childbearing potential (i.e., those not postmenopausal or surgically sterile) must confirm to the best of their knowledge that they are not pregnant or plan to get pregnant
Key exclusion criteria (11 listed)
- Exposure to phenylbutyrate, valproic acid, probenecid, known HDAC inhibitors or other transcriptionally active compounds within 3 months (90 days) prior to the baseline visit
- History of known sensitivity or intolerability to phenylbutyrate, sodium butyrate or sodium acetate
- Existence of a known malignancy that might require treatment during the course of this study
- Exposure to any investigational drug within 30 days of the baseline visit
- Subjects with underlying hematologic, hepatic or renal disease; screening white blood cell (WBC) count less than 3,800/mm3, screening creatinine greater than 2.0 or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal
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 |
|---|---|---|
| sodium phenylbutyrate | Drug | – |
Primary outcome
Proportion of subjects able to complete treatment (Week 16)
15 secondary outcomes
Secondary safety and tolerability outcomes at Weeks 1, 4, 5, 10, 16, & 20 include:
adverse events,
changes in vital signs,
and clinical lab assessments.
Secondary clinical measures at Weeks 4, 10, 16, and 20 include components of the UHDRS:
total motor,
Stroop,
independence,
& total functional capacity.
Secondary biological indicators of treatment affects at Weeks 4, 10, 16, & 20 include:
markers of neuroprotection (e.g. NAA) via MRS,
histone acetylation (levels in WBC; fetal hemoglobin levels in blood),
depletion of glutamine,
gene expression analyses,
and biochemical analyses for pharmacokinetics.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2012.
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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
Co-Chair, Huntington Study Group, Massachusetts General Hospital
Karl Kieburtz, MD, MPH principal investigator
Director, Clinical Trials Coordination Center, University of Rochester
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sodium phenylbutyrate in people with Huntington's Disease, run by University of Rochester at 8 sites in United States.
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 9 inclusion and 11 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: finished, as of the sponsor's last update on 15 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of subjects able to complete treatment (Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Aug 2012.