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Tricaprilin in Mild to Moderate Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tricaprilin
Placebo
Sponsored by
Cerecin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring ketones, Apolipoprotein E, ApoE genotype, cognitive function, glucose metabolism

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • 21st Century Neurology, a division of Xenoscience Inc.
  • Comprehensive NeuroScience
  • Pharmacology Research Institute
  • Pharmacology Research Institute
  • Pharmacology Research Institute
  • The Southwest Institute for Clinical Research
  • Pharmacology Research Institute
  • Baumel-Eisner Neuromedical Institute
  • Meridien Research
  • Baumel-Eisner Neuromedical Institute, Inc.
  • Sunrise Clinical Research
  • Comprehensive NeuroScience
  • Baumel-Eisner Neuromedical Institute
  • Anchor Research Center
  • Renstar Medical Research
  • Comprehensive NeuroScience
  • Meridien Research
  • Meridien Research
  • Radiant Research
  • Multi-Specialty Research Associates of North Carolina
  • Radiant Research
  • Radiant Research
  • Research Across America
  • Radiant Research
  • Grayline Clinical Drug Trials

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

AC-1202

Matching Placebo to AC-1202

Arm Description

Tricaprilin formulation, once daily. Administered orally

Placebo formulation, once daily. Administered orally

Outcomes

Primary Outcome Measures

Number of subjects with treatment related adverse events
AE incidence rate per treatment group

Secondary Outcome Measures

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
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)
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.
Mini-Mental State Exam (MMSE)
Change in MMSE

Full Information

First Posted
September 1, 2005
Last Updated
September 18, 2020
Sponsor
Cerecin
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1. Study Identification

Unique Protocol Identification Number
NCT00142805
Brief Title
Tricaprilin in Mild to Moderate Alzheimer's Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
November 4, 2004 (Actual)
Primary Completion Date
June 29, 2006 (Actual)
Study Completion Date
January 7, 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cerecin

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
ketones, Apolipoprotein E, ApoE genotype, cognitive function, glucose metabolism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
152 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AC-1202
Arm Type
Active Comparator
Arm Description
Tricaprilin formulation, once daily. Administered orally
Arm Title
Matching Placebo to AC-1202
Arm Type
Placebo Comparator
Arm Description
Placebo formulation, once daily. Administered orally
Intervention Type
Drug
Intervention Name(s)
Tricaprilin
Other Intervention Name(s)
AC-1202
Intervention Description
Powder formulation will be mixed in a liquid (approximately 8 oz).
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Matching placebo to AC-1202
Intervention Description
Powder formulation will be mixed in a liquid (approximately 8 oz).
Primary Outcome Measure Information:
Title
Number of subjects with treatment related adverse events
Description
AE incidence rate per treatment group
Time Frame
104 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) profile of tricaprilin
Description
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
Time Frame
Baseline, Day 45, Day 90
Title
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Description
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)
Time Frame
90 days
Title
Clinical Global Impression of Change
Description
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.
Time Frame
90 days
Title
Mini-Mental State Exam (MMSE)
Description
Change in MMSE
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
21st Century Neurology, a division of Xenoscience Inc.
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Comprehensive NeuroScience
City
Cerritos
State/Province
California
ZIP/Postal Code
90703
Country
United States
Facility Name
Pharmacology Research Institute
City
Los Alamitos
State/Province
California
ZIP/Postal Code
90720
Country
United States
Facility Name
Pharmacology Research Institute
City
Newport Beach
State/Province
California
ZIP/Postal Code
92660
Country
United States
Facility Name
Pharmacology Research Institute
City
Northridge
State/Province
California
ZIP/Postal Code
91324
Country
United States
Facility Name
The Southwest Institute for Clinical Research
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Facility Name
Pharmacology Research Institute
City
Riverside
State/Province
California
ZIP/Postal Code
92506
Country
United States
Facility Name
Baumel-Eisner Neuromedical Institute
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Meridien Research
City
Brooksville
State/Province
Florida
ZIP/Postal Code
34613
Country
United States
Facility Name
Baumel-Eisner Neuromedical Institute, Inc.
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33321
Country
United States
Facility Name
Sunrise Clinical Research
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Comprehensive NeuroScience
City
Melbourne
State/Province
Florida
ZIP/Postal Code
32935
Country
United States
Facility Name
Baumel-Eisner Neuromedical Institute
City
Miami Beach
State/Province
Florida
ZIP/Postal Code
33154
Country
United States
Facility Name
Anchor Research Center
City
Naples
State/Province
Florida
ZIP/Postal Code
34102
Country
United States
Facility Name
Renstar Medical Research
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Comprehensive NeuroScience
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33702
Country
United States
Facility Name
Meridien Research
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33709
Country
United States
Facility Name
Meridien Research
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
Facility Name
Radiant Research
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60610
Country
United States
Facility Name
Multi-Specialty Research Associates of North Carolina
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
Facility Name
Radiant Research
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Radiant Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Research Across America
City
Dallas
State/Province
Texas
ZIP/Postal Code
75234
Country
United States
Facility Name
Radiant Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Grayline Clinical Drug Trials
City
Wichita Falls
State/Province
Texas
ZIP/Postal Code
76309
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
6544385
Citation
Blass JP, Zemcov A. Alzheimer's disease. A metabolic systems degeneration? Neurochem Pathol. 1984 Summer;2(2):103-14. doi: 10.1007/BF02834249.
Results Reference
background
PubMed Identifier
8592548
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. doi: 10.1056/NEJM199603213341202.
Results Reference
background
PubMed Identifier
10811879
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. doi: 10.1073/pnas.090106797.
Results Reference
background
PubMed Identifier
9932420
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. doi: 10.1016/s0079-6123(08)64027-3.
Results Reference
background
PubMed Identifier
10634967
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. doi: 10.1002/(sici)1520-7560(199911/12)15:63.0.co;2-8.
Results Reference
background
PubMed Identifier
10805800
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. doi: 10.1073/pnas.97.10.5440.
Results Reference
background
PubMed Identifier
21992747
Citation
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.
Results Reference
derived
PubMed Identifier
19664276
Citation
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.
Results Reference
derived
Links:
URL
http://www.accerapharma.com/
Description
Accera Pharmaceuticals Clinical Trials Query Form

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Tricaprilin in Mild to Moderate Alzheimer's Disease

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