Tricaprilin in Mild to Moderate Alzheimer's Disease

NCT ID: NCT00142805

Last Updated: 2020-09-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

152 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-11-04

Study Completion Date

2007-01-07

Brief Summary

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The purpose of this study is to evaluate the safety, tolerability and effectiveness of tricaprilin administered once a day for ninety days in subjects with mild to moderate, probable Alzheimer's disease.

Detailed Description

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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.

Conditions

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Alzheimer's Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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AC-1202

Tricaprilin formulation, once daily. Administered orally

Group Type ACTIVE_COMPARATOR

Tricaprilin

Intervention Type DRUG

Powder formulation will be mixed in a liquid (approximately 8 oz).

Matching Placebo to AC-1202

Placebo formulation, once daily. Administered orally

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Powder formulation will be mixed in a liquid (approximately 8 oz).

Interventions

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Tricaprilin

Powder formulation will be mixed in a liquid (approximately 8 oz).

Intervention Type DRUG

Placebo

Powder formulation will be mixed in a liquid (approximately 8 oz).

Intervention Type OTHER

Other Intervention Names

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AC-1202 Matching placebo to AC-1202

Eligibility Criteria

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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
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cerecin

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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21st Century Neurology, a division of Xenoscience Inc.

Phoenix, Arizona, United States

Site Status

Comprehensive NeuroScience

Cerritos, California, United States

Site Status

Pharmacology Research Institute

Los Alamitos, California, United States

Site Status

Pharmacology Research Institute

Newport Beach, California, United States

Site Status

Pharmacology Research Institute

Northridge, California, United States

Site Status

The Southwest Institute for Clinical Research

Rancho Mirage, California, United States

Site Status

Pharmacology Research Institute

Riverside, California, United States

Site Status

Baumel-Eisner Neuromedical Institute

Boca Raton, Florida, United States

Site Status

Meridien Research

Brooksville, Florida, United States

Site Status

Baumel-Eisner Neuromedical Institute, Inc.

Fort Lauderdale, Florida, United States

Site Status

Sunrise Clinical Research

Hollywood, Florida, United States

Site Status

Comprehensive NeuroScience

Melbourne, Florida, United States

Site Status

Baumel-Eisner Neuromedical Institute

Miami Beach, Florida, United States

Site Status

Anchor Research Center

Naples, Florida, United States

Site Status

Renstar Medical Research

Ocala, Florida, United States

Site Status

Comprehensive NeuroScience

St. Petersburg, Florida, United States

Site Status

Meridien Research

St. Petersburg, Florida, United States

Site Status

Meridien Research

Tampa, Florida, United States

Site Status

Radiant Research

Chicago, Illinois, United States

Site Status

Multi-Specialty Research Associates of North Carolina

Raleigh, North Carolina, United States

Site Status

Radiant Research

Portland, Oregon, United States

Site Status

Radiant Research

Dallas, Texas, United States

Site Status

Research Across America

Dallas, Texas, United States

Site Status

Radiant Research

San Antonio, Texas, United States

Site Status

Grayline Clinical Drug Trials

Wichita Falls, Texas, United States

Site Status

Countries

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United States

References

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Blass JP, Zemcov A. Alzheimer's disease. A metabolic systems degeneration? Neurochem Pathol. 1984 Summer;2(2):103-14. doi: 10.1007/BF02834249.

Reference Type BACKGROUND
PMID: 6544385 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8592548 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10811879 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9932420 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10634967 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10805800 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21992747 (View on PubMed)

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.

Reference Type DERIVED
PMID: 19664276 (View on PubMed)

Related Links

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http://www.accerapharma.com/

Accera Pharmaceuticals Clinical Trials Query Form

Other Identifiers

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KET-04-001

Identifier Type: -

Identifier Source: org_study_id

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