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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Tricaprilin; Other: Placebo

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: Interventional
• Enrollment (Actual): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • 21st Century Neurology, a division of Xenoscience Inc.
  • California
    • Cerritos, California, United States, 90703
      • Comprehensive Neuroscience
    • Los Alamitos, California, United States, 90720
      • Pharmacology Research Institute
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • Northridge, California, United States, 91324
      • Pharmacology Research Institute
    • Rancho Mirage, California, United States, 92270
      • The Southwest Institute for Clinical Research
    • Riverside, California, United States, 92506
      • Pharmacology Research Institute
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Baumel-Eisner Neuromedical Institute
    • Brooksville, Florida, United States, 34613
      • Meridien Research
    • Fort Lauderdale, Florida, United States, 33321
      • Baumel-Eisner Neuromedical Institute, Inc.
    • Hollywood, Florida, United States, 33021
      • Sunrise Clinical Research
    • Melbourne, Florida, United States, 32935
      • Comprehensive Neuroscience
    • Miami Beach, Florida, United States, 33154
      • Baumel-Eisner Neuromedical Institute
    • Naples, Florida, United States, 34102
      • Anchor Research Center
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Research
    • Saint Petersburg, Florida, United States, 33702
      • Comprehensive Neuroscience
    • Tampa, Florida, United States, 33609
      • Meridien Research
  • Illinois
    • Chicago, Illinois, United States, 60610
      • Radiant Research
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Multi-Specialty Research Associates of North Carolina
  • Oregon
    • Portland, Oregon, United States, 97239
      • Radiant Research
  • Texas
    • Dallas, Texas, United States, 75234
      • Research Across America
    • Dallas, Texas, United States, 75231
      • Radiant Research
    • San Antonio, Texas, United States, 78229
      • Radiant Research
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: AC-1202; Tricaprilin formulation, once daily. Administered orally	Drug: Tricaprilin; Powder formulation will be mixed in a liquid (approximately 8 oz).; Other Names: AC-1202
Placebo Comparator: Matching Placebo to AC-1202; Placebo formulation, once daily. Administered orally	Other: Placebo; Powder formulation will be mixed in a liquid (approximately 8 oz).; Other Names: Matching placebo to AC-1202

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with treatment related adverse events	AE incidence rate per treatment group	104 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Mini-Mental State Exam (MMSE)	Change in MMSE	90 days

Collaborators and Investigators

• Sponsor: Cerecin

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

• Accera Pharmaceuticals Clinical Trials Query Form

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2004
• Primary Completion (Actual): June 29, 2006
• Study Completion (Actual): January 7, 2007

Study Registration Dates

• First Submitted: September 1, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (Estimate): September 2, 2005

Study Record Updates

• Last Update Posted (Actual): September 21, 2020
• Last Update Submitted That Met QC Criteria: September 18, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: cognitive function; Apolipoprotein E; ketones; glucose metabolism; ApoE genotype
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: KET-04-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No