Tricaprilin in Mild to Moderate Alzheimer's Disease

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00142805
• Other study ID #: KET-04-001
• Status: Completed
• Phase: Phase 2
• Start date: November 4, 2004
• Est. completion date: January 7, 2007

Study information

• Verified date: September 2020
• Source: Cerecin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: January 7, 2007
• Est. primary completion date: June 29, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Tricaprilin
Powder formulation will be mixed in a liquid (approximately 8 oz).

Other:
• Placebo
Powder formulation will be mixed in a liquid (approximately 8 oz).

Locations

Country	Name	City	State
United States	Baumel-Eisner Neuromedical Institute	Boca Raton	Florida
United States	Meridien Research	Brooksville	Florida
United States	Comprehensive NeuroScience	Cerritos	California
United States	Radiant Research	Chicago	Illinois
United States	Radiant Research	Dallas	Texas
United States	Research Across America	Dallas	Texas
United States	Baumel-Eisner Neuromedical Institute, Inc.	Fort Lauderdale	Florida
United States	Sunrise Clinical Research	Hollywood	Florida
United States	Pharmacology Research Institute	Los Alamitos	California
United States	Comprehensive NeuroScience	Melbourne	Florida
United States	Baumel-Eisner Neuromedical Institute	Miami Beach	Florida
United States	Anchor Research Center	Naples	Florida
United States	Pharmacology Research Institute	Newport Beach	California
United States	Pharmacology Research Institute	Northridge	California
United States	Renstar Medical Research	Ocala	Florida
United States	21st Century Neurology, a division of Xenoscience Inc.	Phoenix	Arizona
United States	Radiant Research	Portland	Oregon
United States	Multi-Specialty Research Associates of North Carolina	Raleigh	North Carolina
United States	The Southwest Institute for Clinical Research	Rancho Mirage	California
United States	Pharmacology Research Institute	Riverside	California
United States	Comprehensive NeuroScience	Saint Petersburg	Florida
United States	Meridien Research	Saint Petersburg	Florida
United States	Radiant Research	San Antonio	Texas
United States	Meridien Research	Tampa	Florida
United States	Grayline Clinical Drug Trials	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Cerecin

Country where clinical trial is conducted

United States, 

References & Publications (6)

Blass JP, Zemcov A. Alzheimer's disease. A metabolic systems degeneration? Neurochem Pathol. 1984 Summer;2(2):103-14. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with treatment related adverse events	AE incidence rate per treatment group	104 days
Secondary	Pharmacokinetics (PK) profile of tricaprilin	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
Secondary	Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)	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)	90 days
Secondary	Clinical Global Impression of Change	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.	90 days
Secondary	Mini-Mental State Exam (MMSE)	Change in MMSE	90 days

External Links

•   Accera Pharmaceuticals Clinical Trials Query Form