- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00142805
Tricaprilin in Mild to Moderate Alzheimer's Disease
Safety, Tolerability and Efficacy Study of Tricaprilin (AC-1202) Administered for Ninety Days in Subjects With Probable Alzheimer's Disease of Mild to Moderate Severity
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Substantial scientific evidence has shown that defects in glucose metabolism occur in Alzheimer's disease. Attempts to compensate for the reduced cerebral metabolic rates in AD have met with some success. Treatment of AD patients with high doses of glucose and insulin will raise cognitive scores. However, this effect is slight, and high doses of insulin can have adverse consequences. Administration of ketone bodies or their metabolic precursors such as medium chain triglycerides (MCTs) presents an attractive alternative to glucose and insulin. In a preliminary study, tricaprilin, an MCT, demonstrated pharmacological activity and statistically significant efficacy in improving short-term memory and attention performance after a single dose.
Participants will be randomized to receive either tricaprilin or a matching placebo, administered once a day by mixing powder in a glass of liquid. The treatment period will last 90 days, followed by a 2-week washout period. Each patient will be seen 5 times: at screening, baseline, and post-baseline days 45, 90, and 104. The visits will include physical and/or neuropsychological examinations, electrocardiograms (ECGs) and laboratory tests.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Phoenix, Arizona, United States, 85013
- 21st Century Neurology, a division of Xenoscience Inc.
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California
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Cerritos, California, United States, 90703
- Comprehensive Neuroscience
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Los Alamitos, California, United States, 90720
- Pharmacology Research Institute
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Newport Beach, California, United States, 92660
- Pharmacology Research Institute
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Northridge, California, United States, 91324
- Pharmacology Research Institute
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Rancho Mirage, California, United States, 92270
- The Southwest Institute for Clinical Research
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Riverside, California, United States, 92506
- Pharmacology Research Institute
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Florida
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Boca Raton, Florida, United States, 33486
- Baumel-Eisner Neuromedical Institute
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Brooksville, Florida, United States, 34613
- Meridien Research
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Fort Lauderdale, Florida, United States, 33321
- Baumel-Eisner Neuromedical Institute, Inc.
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Hollywood, Florida, United States, 33021
- Sunrise Clinical Research
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Melbourne, Florida, United States, 32935
- Comprehensive Neuroscience
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Miami Beach, Florida, United States, 33154
- Baumel-Eisner Neuromedical Institute
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Naples, Florida, United States, 34102
- Anchor Research Center
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Ocala, Florida, United States, 34471
- Renstar Medical Research
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Saint Petersburg, Florida, United States, 33709
- Meridien Research
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Saint Petersburg, Florida, United States, 33702
- Comprehensive Neuroscience
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Tampa, Florida, United States, 33609
- Meridien Research
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Illinois
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Chicago, Illinois, United States, 60610
- Radiant Research
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North Carolina
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Raleigh, North Carolina, United States, 27609
- Multi-Specialty Research Associates of North Carolina
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Oregon
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Portland, Oregon, United States, 97239
- Radiant Research
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Texas
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Dallas, Texas, United States, 75234
- Research Across America
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Dallas, Texas, United States, 75231
- Radiant Research
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San Antonio, Texas, United States, 78229
- Radiant Research
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Wichita Falls, Texas, United States, 76309
- Grayline Clinical Drug Trials
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Informed Consent Form signed by patient and caregiver
- Diagnosis of probably Alzheimer's disease of mild to moderate severity
- Age 50 or older
- If female, 2 years postmenopausal or surgically sterile
- Hearing, vision, and physical abilities adequate to perform assessments (corrective aids allowed)
- Caregiver to attend all visits, perform assessments, and supervise administration of study medication
- CT or MRI within 24 months prior to screening compatible with a diagnosis of probably Alzheimer's disease
- Modified Hachinski Ischemia Scale score of 4 or less
- ADAS-Cog score between 15 and 35 inclusive at screening
- MMSE score between 14 and 24 inclusive at screening
- Stable medical condition for 3 consecutive months immediately prior to baseline
- No clinically significant abnormal findings on the physical examination, medical history, or clinical laboratory results during screening
Exclusion Criteria:
- Any condition that would, in the opinion of the Principal Investigator, render the patient or the caregiver unsuitable for the study, or place them at substantial risk of adverse outcome
- Unwillingness or inability of the patient and/or caregiver to fulfill the requirements of the study
- Resident in a skilled nursing facility
- Any significant neurological disease other than probable AD (e.g. Parkinson's disease, Huntington's disease, brain tumor, normal pressure hydrocephalus, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, history of stroke, or history of head injury requiring hospitalization)
- An alternate cause for dementia other than AD as determined by a required CT or MRI scan within 24 months prior to screening
- Current history of major psychiatric disorder
- Major depression as determined by a Cornell Scale for Depression in Dementia
- Clinically significant hypothyroidism
- Clinically significant B12 deficiency
- Unstable or clinically significant cardiovascular disease
- Diabetes of any type
- History of tertiary syphilis
- Cancer within 3 years prior to baseline, with the exception of squamous and basal cell carcinoma
- Vital sign abnormalities
- Clinically significant renal disease or insufficiency
- Clinically significant hepatic disease or insufficiency
- Alcohol consumption greater than 2 oz of spirits per day or 14 oz per week (1 oz of spirits is equal to 6 oz of wine or 12 oz of beer)
- Current history of alcohol abuse or other substance abuse within 24 months prior to baseline
- Known HIV infection
- Use of any investigational compound within 30 days prior to screening
- Use of prohibited medications (contact site for details)
- Prior or current use of medium-chain triglycerides (MCTs) for medical purposes
- Known allergies to coconut oil
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: AC-1202
Tricaprilin formulation, once daily.
Administered orally
|
Powder formulation will be mixed in a liquid (approximately 8 oz).
Other Names:
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Placebo Comparator: Matching Placebo to AC-1202
Placebo formulation, once daily.
Administered orally
|
Powder formulation will be mixed in a liquid (approximately 8 oz).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of subjects with treatment related adverse events
Time Frame: 104 days
|
AE incidence rate per treatment group
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104 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics (PK) profile of tricaprilin
Time Frame: Baseline, Day 45, Day 90
|
Correlations between the Cmax serum BHB level on Day 90 and the change from baseline total score for the three efficacy scales was determined by the Pearson correlation statistics
|
Baseline, Day 45, Day 90
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Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Time Frame: 90 days
|
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog 11) is an 11- item cognitive subscale that objectively measures memory, language, orientation, and praxis with a total score range of 0 (no impairment) to 70 (severe impairment)
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90 days
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Clinical Global Impression of Change
Time Frame: 90 days
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Clinician's global impression rated with Alzheimer's Disease cooperative Study - Clinical Global Impression of Change (ADCS-CGIC).
The rating is from marked improvement to marked worsening.
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90 days
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Mini-Mental State Exam (MMSE)
Time Frame: 90 days
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Change in MMSE
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90 days
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999 Nov-Dec;15(6):412-26. doi: 10.1002/(sici)1520-7560(199911/12)15:63.0.co;2-8.
- Blass JP, Zemcov A. Alzheimer's disease. A metabolic systems degeneration? Neurochem Pathol. 1984 Summer;2(2):103-14. doi: 10.1007/BF02834249.
- Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996 Mar 21;334(12):752-8. doi: 10.1056/NEJM199603213341202.
- Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6037-42. doi: 10.1073/pnas.090106797.
- Swaab DF, Lucassen PJ, Salehi A, Scherder EJ, van Someren EJ, Verwer RW. Reduced neuronal activity and reactivation in Alzheimer's disease. Prog Brain Res. 1998;117:343-77. doi: 10.1016/s0079-6123(08)64027-3.
- Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5440-4. doi: 10.1073/pnas.97.10.5440.
- Henderson ST, Poirier J. Pharmacogenetic analysis of the effects of polymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic on cognition in mild to moderate Alzheimer's disease; a randomized, double-blind, placebo-controlled study. BMC Med Genet. 2011 Oct 12;12:137. doi: 10.1186/1471-2350-12-137.
- Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 2009 Aug 10;6:31. doi: 10.1186/1743-7075-6-31.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- KET-04-001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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