Keywords:Huntington's Disease (HD) , CREST-E , Creatine Treatment Trial , Multi-Center
The is a controlled (double-blind) multi-center Phase III safety, tolerability, and efficacy trial of 40-grams daily creatine in Huntington’s disease (HD) patients. Creatine monohydrate (“creatine”) is a nutritional supplement that can support the production of cellular energy.
The primary goal of this study will be to assess the effects of creatine monohydrate on the progression of functional decline in HD as measured by the annulazied rate of change in the Total Functional Capacity (TFC) scale. Secondarily, we will aim to examine the long term safety and tolerability of creatine monohydrate and to determine whether its effects correspond to measures of bioavailability, improvement of oxidative injury biomarkers, or reduction of brain atrophy. The design of this study will incorporate interim analyses of safety, futility, and efficacy to provide early and repeated safety data for the FDA at high doses and permit early stopping or modification, if necessary.
Male or female age 18 or older.
Subjects must have clinical features of HD and a confirmatory family
history of HD; OR CAG repeat expansion ≥ 36.
Subjects in Stage I or II of illness (TFC ≥ 7).
Subjects must be ambulatory and not requiring skilled nursing care
at the time of enrollment.
Women of childbearing potential (i.e., those not postmenopausal or
surgically sterile) must have a negative pregnancy test, be nonlactating and use adequate contraception methods during the study.
Adequate birth control includes: abstinence; oral, implanted or
injected contraceptives, e.g., birth control pills; intra-uterine device;
barrier (e.g., vaginal ring or diaphragm/cervical cap with spermicide; transdermal patch and/or partner vasectomy). Reliable
contraception must have been in use 30 days prior to the Baseline
Subjects must be capable of providing informed consent and
complying with trial procedures.
Subjects must be able to take oral drug.
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/day
within 30 days of randomization (Baseline visit).
Use of supplemental Coenzyme Q10 at a dose greater than 600
milligrams daily within 30 days of randomization (Baseline visit).
Screening creatinine greater than 2.0 mg/dL.
Screening laboratory abnormalities that in the judgment of the
investigator would jeopardize safe conduct of study.
Current or history of substance (alcohol or drug) abuse within one
year of randomization (Baseline visit).
Clinical evidence of unstable medical illness in the investigator’s
Clinical evidence of unstable psychiatric illness defined as psychosis
(hallucinations or delusions), untreated major depression or suicidal ideation within 90 days randomization (Baseline visit).
Additional Exclusion Criteria for Imaging Sites:
Previously obtained MRI scans with evidence of infection, infarction
or other focal lesions.
Presence of pacemakers, aneurysm clips, artificial heart valves, ear
implants, metal fragments or foreign objects in the eyes, skin or
body or any other known contra-indication to MRI.