Alzheimer's DiseasePhase 2NCT00142805
Tricaprilin in Mild to Moderate Alzheimer's Disease
A Phase 2 study testing Tricaprilin in people with Alzheimer's Disease, run by Cerecin at 25 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Tricaprilin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 25 sitesUnited States
- Study dates
- 4 Nov 2004to 7 Jan 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
Baumel-Eisner Neuromedical Institute
Boca Raton, Florida, 33486
Meridien Research
Brooksville, Florida, 34613
Comprehensive NeuroScience
Cerritos, California, 90703
Radiant Research
Chicago, Illinois, 60610
Radiant Research
Dallas, Texas, 75231
Research Across America
Dallas, Texas, 75234
Baumel-Eisner Neuromedical Institute, Inc.
Fort Lauderdale, Florida, 33321
Sunrise Clinical Research
Hollywood, Florida, 33021
Pharmacology Research Institute
Los Alamitos, California, 90720
Comprehensive NeuroScience
Melbourne, Florida, 32935
Baumel-Eisner Neuromedical Institute
Miami Beach, Florida, 33154
Anchor Research Center
Naples, Florida, 34102
Pharmacology Research Institute
Newport Beach, California, 92660
Pharmacology Research Institute
Northridge, California, 91324
Renstar Medical Research
Ocala, Florida, 34471
21st Century Neurology, a division of Xenoscience Inc.
Phoenix, Arizona, 85013
Radiant Research
Portland, Oregon, 97239
Multi-Specialty Research Associates of North Carolina
Raleigh, North Carolina, 27609
The Southwest Institute for Clinical Research
Rancho Mirage, California, 92270
Pharmacology Research Institute
Riverside, California, 92506
Radiant Research
San Antonio, Texas, 78229
Comprehensive NeuroScience
St. Petersburg, Florida, 33702
Meridien Research
St. Petersburg, Florida, 33709
Meridien Research
Tampa, Florida, 33609
Grayline Clinical Drug Trials
Wichita Falls, Texas, 76309
About this study
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
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.
Read the 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.
- Conditions
- Alzheimer's Disease
- Being tested
- Tricaprilin, Placebo
- Keywords
- ketones, Apolipoprotein E, ApoE genotype, cognitive function, glucose metabolism
- Medical subject headings
- Alzheimer Disease, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TricaprilinDrug
Also called AC-1202
Powder formulation will be mixed in a liquid (approximately 8 oz).
PlaceboOther
Also called Matching placebo to AC-1202
Powder formulation will be mixed in a liquid (approximately 8 oz).
| Study group | Role | What they receive |
|---|---|---|
| AC-1202 | Active comparator | Tricaprilin formulation, once daily. Administered orally Receives: Drug: Tricaprilin |
| Matching Placebo to AC-1202 | Placebo comparator | Placebo formulation, once daily. Administered orally Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with treatment related adverse events
AE incidence rate per treatment group
Measured: 104 days
Secondary outcomes (4)
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
Measured: 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)
Measured: 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.
Measured: 90 days
Mini-Mental State Exam (MMSE)
Change in MMSE
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2005 (estimated)
- Study start4 Nov 2004
- Primary completion29 Jun 2006
- Study completion7 Jan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cerecin
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00142805
- Sponsor's protocol ID
- KET-04-001
- Status last verified
- Sep 2020
- First submitted
- 1 Sep 2005
- Last updated
- 21 Sep 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Blass JP, Zemcov A. Alzheimer's disease. A metabolic systems degeneration? Neurochem Pathol. 1984 Summer;2(2):103-14. doi: 10.1007/BF02834249.
PubMed 6544385Reiman 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.
PubMed 8592548Small 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.
PubMed 10811879Swaab 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.
PubMed 9932420Laffel 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.
PubMed 10634967Kashiwaya 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.
PubMed 10805800Henderson 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.
PubMed 21992747Henderson 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.
PubMed 19664276
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00142805
- Acronym / sponsor ID
- KET-04-001
- Conditions
- Alzheimer's Disease
- Keywords
- ketones, Apolipoprotein E, ApoE genotype, cognitive function, glucose metabolism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- CerecinIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2004 (actual)
- Primary completion
- 29 Jun 2006 (actual)
- Study completion
- 7 Jan 2007 (actual)
- First posted
- 2 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AC-1202 | Active comparator | Drug: TricaprilinTricaprilin formulation, once daily. Administered orally |
| Matching Placebo to AC-1202 | Placebo comparator | Other: PlaceboPlacebo formulation, once daily. Administered orally |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TricaprilinAlso: AC-1202Powder formulation will be mixed in a liquid (approximately 8 oz). | Drug | AC-1202 |
| PlaceboAlso: Matching placebo to AC-1202Powder formulation will be mixed in a liquid (approximately 8 oz). | Other | Matching Placebo to AC-1202 |
Primary outcome
Number of subjects with treatment related adverse events
Time frame: 104 days
AE incidence rate per treatment group
4 secondary outcomes
Pharmacokinetics (PK) profile of tricaprilin
Time frame: Baseline, Day 45, Day 90
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
Time frame: 90 days
Clinical Global Impression of Change
Time frame: 90 days
Mini-Mental State Exam (MMSE)
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2020.
- Background: PubMed 6544385Blass JP, Zemcov A. Alzheimer's disease. A metabolic systems degeneration? Neurochem Pathol. 1984 Summer;2(2):103-14. doi: 10.1007/BF02834249.
- Background: PubMed 8592548Reiman 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.
- Background: PubMed 10811879Small 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.
- Background: PubMed 9932420Swaab 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.
- Background: PubMed 10634967Laffel 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.
- Background: PubMed 10805800Kashiwaya 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.
- Derived from this study: PubMed 21992747Henderson 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.
- Derived from this study: PubMed 19664276Henderson 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.
- Accera Pharmaceuticals Clinical Trials Query FormLink provided by the sponsor.
Related trials for Alzheimer's Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tricaprilin in people with Alzheimer's Disease, run by Cerecin at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with treatment related adverse events (time frame: 104 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00142805, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2020.