Trial Outcomes & Findings for Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia (NCT NCT00545974)

Last Updated: 2020-11-17

Results Overview

NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. A screening question is asked about each sub-domain. If the responses to these questions indicate that the patient has problems with a particular sub-domain of behavior, the caregiver is only then asked all the questions about that domain, rating the frequency of the symptoms on a 4-point scale, their severity on a 3-point scale, and the distress the symptom causes them on a 5-point scale. Severity(1=Mild to 3=Severe),frequency(1=occasionally to 4=very frequently) scales recorded for each domain; frequency\*severity=each domain score(range 0-12). Total score=sum of each domain score(range 0-144);higher score=greater behavioral disturbances;negative change score from baseline=improvement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

81 participants

Primary outcome timeframe

Baseline, 26 weeks

Results posted on

2020-11-17

Participant Flow

We recruited patients from nine US academic dementia research centres with expertise in the diagnosis of FTD. Study visits occurred between December 12, 2007, and May 7, 2012.

100 subjects were assessed for eligibility. 19 were excluded prior to randomization. 81 were randomized. 16 subjects did not meet inclusion criteria and 3 declined to participate.

Participant milestones

Participant milestones
Measure	Memantine Memantine 10mg administered orally twice daily	Placebo Placebo (inactive tablets identical to memantine 10mg tablets)
Overall Study STARTED	39	42
Overall Study COMPLETED	37	39
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Memantine n=39 Participants Memantine 10mg administered orally twice daily	Placebo n=42 Participants Placebo (inactive tablets identical to memantine 10mg tablets)	Total n=81 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	18 Participants n=5 Participants	25 Participants n=7 Participants	43 Participants n=5 Participants
Age, Categorical >=65 years	21 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants
Age, Continuous	65.8 years STANDARD_DEVIATION 2.8 • n=5 Participants	66.2 years STANDARD_DEVIATION 2.3 • n=7 Participants	66.0 years STANDARD_DEVIATION 2.5 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	10 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	32 Participants n=7 Participants	51 Participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants	42 participants n=7 Participants	81 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 26 weeks

Outcome measures

Outcome measures
Measure	Memantine n=37 Participants Memantine 10mg administered orally twice daily	Placebo n=39 Participants Placebo (inactive tablets identical to memantine 10mg tablets)
Change in Neuropsychiatric Inventory (NPI)	-1.9 units on a scale Interval -6.1 to 2.3	0.3 units on a scale Interval -4.0 to 4.7

PRIMARY outcome

Timeframe: 26 Weeks

The scale is rated on a 7-point scale, using a range of responses from 1 (very much improved) through 7 (very much worse). The clinician compares the participant's current condition to the condition at admission to the project.

Outcome measures

Outcome measures
Measure	Memantine n=37 Participants Memantine 10mg administered orally twice daily	Placebo n=39 Participants Placebo (inactive tablets identical to memantine 10mg tablets)
Clinical Global Impression of Change (CGIC)	4.4 units on a scale Interval 3.7 to 5.2	4.8 units on a scale Interval 4.8 to 5.1

SECONDARY outcome

Timeframe: Baseline and 26 Weeks

Clinical dementia rating sum of boxes CDR-SB (0-18) high scores indicate high impairment. Functional activities questionnaire FAQ (0-30) high scores indicate high impairment. Texas functional living scale TFLS (0 to 52) high scores suggest better instrumental activities of daily living functioning. Mini-Mental State Examination MMSE (0-30) low scores indicate low cognition. The executive interview EXIT25 (0 to 50) high scores indicate more executive impairment. A modified unified Parkinson's disease rating scale UPDRS (0-199) high scores indicate worse disability. Boston naming test (0-15) low scores indicate more retrieval difficulties.

Outcome measures

Outcome measures
Measure	Memantine n=37 Participants Memantine 10mg administered orally twice daily	Placebo n=39 Participants Placebo (inactive tablets identical to memantine 10mg tablets)
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test CDR-SB	1.5 units on a scale Interval 0.9 to 2.1	1.5 units on a scale Interval 0.8 to 2.1
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test UPDRS	1.7 units on a scale Interval -0.1 to 3.4	1.4 units on a scale Interval -0.7 to 3.4
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test FAQ	4.3 units on a scale Interval 2.7 to 6.0	2.9 units on a scale Interval 1.0 to 4.7
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test TFLS	-3.7 units on a scale Interval -5.7 to -1.7	-2.8 units on a scale Interval -4.4 to -1.1
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test MMSE	-1.2 units on a scale Interval -2.5 to 0.1	-0.9 units on a scale Interval -1.8 to 0.0
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test EXIT25	1.9 units on a scale Interval -0.1 to 3.9	0.7 units on a scale Interval -1.1 to 2.4
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: CDR-SB, FAQ, TFLS, MMSE, EXIT25, UPDRS, Boston Naming Test Boston naming test	-1.4 units on a scale Interval -2.9 to 0.0	0.7 units on a scale Interval 0.3 to 1.2

SECONDARY outcome

Timeframe: Baseline and 26 Weeks

Letter fluency, score is number of words recalled starting with a specified letter for 60 seconds. There are 3 trials, with 3 different letters. The total number of correct responses is totaled for all 3 trials for the score. Low scores indicate high impairment Category fluency, score is number of items generated belonging to a specific category (such as animals) in 60 seconds, low scores indicate high impairment. Digit symbol, score is number of symbols that correctly corresponded to the random numerals entered in the form in 90 seconds. Participants are given a table of numerals with matching symbols, and a form with random numerals with open spaces. Low scores indicate high impairment. Digits backwards, score is number of digits backwards recalled (range: 0-14), The participant hears a list of digits and is asked to repeat the digits backwards. Low scores indicate high impairment.

Outcome measures

Outcome measures
Measure	Memantine n=37 Participants Memantine 10mg administered orally twice daily	Placebo n=39 Participants Placebo (inactive tablets identical to memantine 10mg tablets)
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: Letter Fluency, Category Fluency, Digit Symbol, Digits Backwards Letter fluency	-0.1 number of items recalled Interval -1.2 to 1.1	-0.3 number of items recalled Interval -1.1 to 0.4
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: Letter Fluency, Category Fluency, Digit Symbol, Digits Backwards Category fluency	-0.5 number of items recalled Interval -1.9 to 0.9	-0.7 number of items recalled Interval -2.7 to 1.3
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: Letter Fluency, Category Fluency, Digit Symbol, Digits Backwards Digit symbol	-3.9 number of items recalled Interval -7.5 to -0.3	4.2 number of items recalled Interval 1.7 to 10.1
Longitudinal Changes From Baseline to 26 Weeks for Test Battery: Letter Fluency, Category Fluency, Digit Symbol, Digits Backwards Digits backwards	0.1 number of items recalled Interval -0.3 to 0.5	-0.2 number of items recalled Interval -0.5 to 0.2

SECONDARY outcome

Timeframe: 26 weeks

Outcome measures

Outcome measures
Measure	Memantine n=37 Participants Memantine 10mg administered orally twice daily	Placebo n=39 Participants Placebo (inactive tablets identical to memantine 10mg tablets)
Number of Participants Starting Antipsychotic Therapy	1 Participants	2 Participants

Adverse Events

Memantine

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Memantine n=39 participants at risk Memantine 10mg administered orally twice daily	Placebo n=42 participants at risk Placebo (inactive tablets identical to memantine 10mg tablets)
Gastrointestinal disorders diverticulitis leading to hospital admission	0.00% 0/39	2.4% 1/42
Nervous system disorders vasovagal episode	0.00% 0/39	2.4% 1/42
Nervous system disorders right-sided facial weakness and loss of consciousness	2.6% 1/39	0.00% 0/42

Other adverse events

Other adverse events
Measure	Memantine n=39 participants at risk Memantine 10mg administered orally twice daily	Placebo n=42 participants at risk Placebo (inactive tablets identical to memantine 10mg tablets)
General disorders fatigue	2.6% 1/39	2.4% 1/42
Psychiatric disorders language problems	7.7% 3/39	0.00% 0/42
Psychiatric disorders memory loss	5.1% 2/39	0.00% 0/42
Gastrointestinal disorders diverticulitis	0.00% 0/39	4.8% 2/42
Gastrointestinal disorders nausea	0.00% 0/39	7.1% 3/42
Injury, poisoning and procedural complications abrasion	5.1% 2/39	0.00% 0/42
Injury, poisoning and procedural complications fall	12.8% 5/39	4.8% 2/42
Nervous system disorders dizziness	5.1% 2/39	4.8% 2/42
Nervous system disorders headache	2.6% 1/39	7.1% 3/42
Nervous system disorders agitation	0.00% 0/39	4.8% 2/42
Nervous system disorders back pain	5.1% 2/39	0.00% 0/42
Psychiatric disorders behavioral rigidity	2.6% 1/39	2.4% 1/42
Psychiatric disorders inappropriate sexual behavior	0.00% 0/39	9.5% 4/42
Psychiatric disorders insomnia	0.00% 0/39	9.5% 4/42
Psychiatric disorders obsessive compulsive symptoms	5.1% 2/39	2.4% 1/42
Psychiatric disorders somnolence	2.6% 1/39	2.4% 1/42
Renal and urinary disorders urinary tract infection	5.1% 2/39	0.00% 0/42
Respiratory, thoracic and mediastinal disorders upper respiratory infection	5.1% 2/39	0.00% 0/42
Renal and urinary disorders urinary frequency	2.6% 1/39	2.4% 1/42
Skin and subcutaneous tissue disorders rash	2.6% 1/39	2.4% 1/42

Additional Information

Dr. Adam L. Boxer

UCSF Memory and Aging Center

Phone: 4154760668

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place