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Feasibility Study in Subjects With Mild to Moderate Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT02560753
Recruitment Status : Completed
First Posted : September 25, 2015
Results First Posted : July 30, 2018
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
T3D Therapeutics, Inc.

Brief Summary:

The study is a randomized, parallel, 4-dose design in subjects with mild-to-moderate Alzheimer's Disease. Subjects will be randomized to one of 4 doses of T3D-959. Subjects will be evaluated for changes from baseline in cerebral metabolic rate of glucose (FDG-PET imaging), functional connectivity of the hippocampus (BOLD-fMRI), and cognitive function (ADAS-Cog11 and DSST) as well as assessed for safety and tolerability to T3D-959.

An expanded access extension is planed to provide access to study medication to subjects who have completed the main study and requested continued use.


Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: T3D-959 Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2a Feasibility Study of T3D-959 in Subjects With Mild to Moderate Alzheimer's Disease
Study Start Date : July 2015
Actual Primary Completion Date : May 30, 2016
Actual Study Completion Date : June 30, 2016


Arm Intervention/treatment
Experimental: T3D-959 3mg
Nine subjects will take 3mg by mouth once daily for two weeks, with or without food.
Drug: T3D-959
The 3mg dosage is supplied as 1mg capsules (three capsules, taken once daily by mouth) The 10mg dosage is supplied as 5mg capsules (two capsules, taken once daily by mouth) The 30mg dosage is supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth) The 90mg dosage is supplied as 15mg capsules (six capsules, taken once daily by mouth)

Experimental: T3D-959 10mg
Nine subjects will take 10mg by mouth once daily for two weeks, with or without food.
Drug: T3D-959
The 3mg dosage is supplied as 1mg capsules (three capsules, taken once daily by mouth) The 10mg dosage is supplied as 5mg capsules (two capsules, taken once daily by mouth) The 30mg dosage is supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth) The 90mg dosage is supplied as 15mg capsules (six capsules, taken once daily by mouth)

Experimental: T3D-959 30mg
Nine subjects will take 30mg by mouth once daily for two weeks, with or without food.
Drug: T3D-959
The 3mg dosage is supplied as 1mg capsules (three capsules, taken once daily by mouth) The 10mg dosage is supplied as 5mg capsules (two capsules, taken once daily by mouth) The 30mg dosage is supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth) The 90mg dosage is supplied as 15mg capsules (six capsules, taken once daily by mouth)

Experimental: T3D-959 90mg
Nine subjects will take 90mg by mouth once daily for two weeks, with or without food.
Drug: T3D-959
The 3mg dosage is supplied as 1mg capsules (three capsules, taken once daily by mouth) The 10mg dosage is supplied as 5mg capsules (two capsules, taken once daily by mouth) The 30mg dosage is supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth) The 90mg dosage is supplied as 15mg capsules (six capsules, taken once daily by mouth)




Primary Outcome Measures :
  1. Change From Baseline (End of Treatment - Baseline) for FDG-PET Imaging With Whole Brain and White Matter as Reference Region [ Time Frame: after 14 days of treatment ]
    Changes in relative brain glucose metabolism (delta R CMRgl) were measured by FDG-PET. At each time point, a ratio of the PET reading in a pre-defined region of interest (sROI), known to be affected by AD, and in a reference region (RR) that is spared in AD, is determined. This ratio is defined as "sROI index" (spared region). A second RR, brain white matter (WM), was also used in this calculation: sROI index" (WM) value. delta sROI is defined as change in the sROI index values, over the treatment period. In this study we are looking for changes in delta sROI with increasing doses of T3D-959. Dose dependent changes in delta sROI (AD spared) are compared to those observed with the WM as the RR: delta sROI (WM). Dose related changes in delta sROI suggests T3D-959 is entering the brain and effecting glucose metabolism in a dose dependent fashion.

  2. The Effect of Treatment With T3D-959 on Changes in Resting State Blood Oxygen Level Dependent (BOLD) Signal in Functional Magnetic Resonance Imaging (fMRI) of the Brain Areas Associated With Cognitive Tasks. [ Time Frame: after 14 days of treatment ]
    Changes in BOLD fMRI parameters such as GoF (see Study Description) over the course of two weeks of treatment, were obtained in this study. BOLD fMRI has been used in cross sectional and longitudinal studies of Alzheimer's subjects, for instance in the Alzheimer's Disease Neuroimaging Initiative studies. However, no studies monitoring Default Mode Networks measured parameters such as GoF, in the context of an effective AD therapeutic, as a result it is difficult to interpret the observed small changes listed in BOLD fMRI parameters obtained in this trial. Instead the changes in the listed BOLD fMRI parameters (EOT - BL) are reported without interpretation. These values represent changes in fMRI connectivity patterns over time and are unitless.


Secondary Outcome Measures :
  1. Change From Baseline in the Score of the Digit Symbol Substitution Test [ Time Frame: after 14 days of treatment ]
    The digit symbol substitution test assesses attention, psychomotor speed, complex scanning, visual tracking, and immediate memory. This test consists of 4 rows each with 25 small blank squares; above each square is a number between 1 and 9. At the top is a 'key,' which pairs each number (1 through 9) with an unfamiliar symbol. The participant has 90 seconds to work as quickly as possible (left to right across the rows) to fill in each blank square with the appropriate symbol based on the number above the square. Results are presented as total number correct; therefore, lower numbers indicate greater impairment. Scores on the DSST range from 0-93.

  2. Change From Baseline in the Total Score of the 11-item Alzheimer's Disease Assessment Scale - Cognitive Subscale [ Time Frame: after 14 days of treatment ]
    The 11-item Alzheimer's Disease Assessment Scale (ADAS-Cog 11) is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. The score can range between 0 and 70. A higher score indicates more cognitive impairment. A positive change in the score indicates cognitive worsening. The minimum severity score is 0 and the maximum severity score is 70.


Other Outcome Measures:
  1. Safety and Tolerability of Treatment With T3D-959 Over a 2-week Period in Subjects With Mild-to-moderate AD. New [ Time Frame: after 14 days of treatment ]
    Number of participants with treatment related adverse events (AEs) as assessed by analysis of adverse events, including symptoms, and abnormal findings on physical and neurological examinations, and standard labs.



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets criteria for mild-to-moderate AD with Mini-Mental State Examination (MMSE) score of 14 through 26
  • Clinical Dementia Rating = 0.5 to 2.0
  • Modified Hachinski less than or equal to 4
  • A clinical diagnosis of AD per NINCDS-ADRDA criteria
  • Washout of psychoactive medication (other than anti-depressants): at least 4 weeks prior to baseline
  • Stability of all permitted medications for 4-12 weeks prior to baseline
  • Visual and auditory acuity adequate for neuropsychological testing
  • Home monitoring available for supervision of medications

Exclusion Criteria:

  • Unstable diabetes or insulin use
  • Unable to participate in FDG-PET scanning
  • Inability to undergo a clinical MRI of the brain
  • Diagnosis of significant neurological/psychiatric disease other than AD
  • History of moderate or severe congestive heart failure, NYHA class III or IV, within 12 months prior to baseline.
  • Previous cardiovascular event within the past 6 months prior to baseline
  • Subject is pregnant, or lactating.
  • ALT and/or AST levels that are twice the upper limit of normal; bilirubin levels that exceed 2 mg/dL; serum creatinine >1.5 mg/dL in men or > 1.4 mg/dL in women.
  • Current or history of severe or unstable disorder (medical or psychiatric) requiring treatment that may make the subject unlikely to complete the study.
  • Current use of fluvoxamine.
  • Current unstable use of warfarin.
  • Current use (within 30 days of baseline, visit 2) of certain highly protein-bound medications
  • Malignancy within the last 5 years (other than non-melanoma skin cancer, stable, non-progressive prostate cancer not requiring treatment or in situ cervical cancer).
  • Known history of HIV, hepatitis B, or hepatitis C.
  • Blood pressure greater than 160/100 mmHg.
  • Known or suspected intolerance or hypersensitivity to the study drugs, closely related compounds, or any of their stated ingredients.
  • History of alcohol, drug abuse or dependence (except nicotine dependence) within 2 years.
  • Investigational amyloid lowering therapies use within two months prior to baseline
  • Have participated in any other investigational study or received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to baseline
  • Any surgical or medical condition which may significantly alter the absorption of any drug substance
  • Resides in hospital or moderate to high dependency continuous care facility.
  • Non ambulatory, or wheelchair-bound
  • History of swallowing difficulties.
  • Evidence of clinically relevant pathology that in the investigator's opinion could interfere with the study results or put the subject's safety at risk.

Expanded Access Extension :

Subjects must continue to meet the main study inclusion/exclusion criteria to insure continued safety to continue on a 6 months study extension


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02560753


Locations
United States, Florida
Brain Matters Research
Delray Beach, Florida, United States, 33445
Miami Jewish Health Systems
Miami, Florida, United States, 33137
United States, North Carolina
New Hope Clinical Research
Charlotte, North Carolina, United States, 28204
Sponsors and Collaborators
T3D Therapeutics, Inc.
Investigators
Study Chair: John Didsbury, Ph.D. T3DTherapeutics, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: T3D Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02560753     History of Changes
Other Study ID Numbers: T3D959-201
First Posted: September 25, 2015    Key Record Dates
Results First Posted: July 30, 2018
Last Update Posted: July 30, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders