Trial Outcomes & Findings for Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects (NCT NCT00935493)
NCT ID: NCT00935493
Last Updated: 2014-08-13
Results Overview
The primary outcome measure (PEF6\_Z) is the mean of z-scores for 6 executive function tasks (CANTAB: Spatial Working Memory, Stockings of Cambridge, Intradimensiona/Extradimensional Shift, Paired Associates Learning; Stroop Color Word Score, Trail Making Test - B). The score is composed of six component scales coded as z scores that measures cognitive functioning in which higher scores represent better cognitive functioning; therefore, the least squares means listed here represent mean outcome changes from baseline
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
154 participants
Primary outcome timeframe
12 weeks
Results posted on
2014-08-13
Participant Flow
154 subjects were screened, of which 135 were eligible. Of the 135 eligible, 12 withdrew consent and therefore 123 were randomized.
Participant milestones
| Measure |
Guanfacine 0.1 mg po Qhs
Guanfacine: Guanfacine 0.1 mg po qhs
|
Guanfacine 0.5 mg po Qhs
Guanfacine: Guanfacine 0.5 mg po qhs
|
Placebo po Qhs
Placebo: Placebo po qhs
|
|---|---|---|---|
|
Overall Study
STARTED
|
41
|
41
|
41
|
|
Overall Study
COMPLETED
|
40
|
39
|
40
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
1
|
Reasons for withdrawal
| Measure |
Guanfacine 0.1 mg po Qhs
Guanfacine: Guanfacine 0.1 mg po qhs
|
Guanfacine 0.5 mg po Qhs
Guanfacine: Guanfacine 0.5 mg po qhs
|
Placebo po Qhs
Placebo: Placebo po qhs
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
1
|
|
Overall Study
Treatment Discontinued
|
0
|
1
|
0
|
Baseline Characteristics
Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects
Baseline characteristics by cohort
| Measure |
Guanfacine 0.1 mg po Qhs
n=41 Participants
Guanfacine: Guanfacine 0.1 mg po qhs
|
Guanfacine 0.5 mg po Qhs
n=41 Participants
Guanfacine: Guanfacine 0.5 mg po qhs
|
Placebo po Qhs
n=41 Participants
Placebo: Placebo po qhs
|
Total
n=123 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
80.0 years
STANDARD_DEVIATION 4.0 • n=5 Participants
|
80.1 years
STANDARD_DEVIATION 4.0 • n=7 Participants
|
80.5 years
STANDARD_DEVIATION 4.0 • n=5 Participants
|
80.2 years
STANDARD_DEVIATION 4.0 • n=4 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
54 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
69 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: 119 of the 123 trial participants had outcome data recorded at 12 weeks follow-up.
The primary outcome measure (PEF6\_Z) is the mean of z-scores for 6 executive function tasks (CANTAB: Spatial Working Memory, Stockings of Cambridge, Intradimensiona/Extradimensional Shift, Paired Associates Learning; Stroop Color Word Score, Trail Making Test - B). The score is composed of six component scales coded as z scores that measures cognitive functioning in which higher scores represent better cognitive functioning; therefore, the least squares means listed here represent mean outcome changes from baseline
Outcome measures
| Measure |
Guanfacine 0.1 mg
n=40 Participants
Guanfacine: Guanfacine 0.1 mg
|
Guanfacine 0.5 mg
n=39 Participants
Guanfacine: Guanfacine 0.5 mg
|
Placebo
n=40 Participants
Placebo: Placebo
|
|---|---|---|---|
|
Mean in the Prefrontal Executive Function Z-score (PEF6_6)
|
0.121 Z-score
Standard Error 0.056
|
0.213 Z-score
Standard Error 0.056
|
0.270 Z-score
Standard Error 0.056
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: 119 of the 123 trial participants had outcome data recorded at 12 weeks of follow-up
The seven-point scale was collapsed into 3 groups and coded as a three-level ordinal scale of global status, representing ordered levels of worse (including minimally, moderately and markedly worse), unchanged, and improved (including minimally, moderately, and markedly improved) global status.
Outcome measures
| Measure |
Guanfacine 0.1 mg
n=40 Participants
Guanfacine: Guanfacine 0.1 mg
|
Guanfacine 0.5 mg
n=39 Participants
Guanfacine: Guanfacine 0.5 mg
|
Placebo
n=40 Participants
Placebo: Placebo
|
|---|---|---|---|
|
Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)
Worse
|
4 participants
|
2 participants
|
3 participants
|
|
Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)
No Change
|
20 participants
|
22 participants
|
25 participants
|
|
Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)
Improved
|
16 participants
|
15 participants
|
12 participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: 119 of the 123 trial participants had outcome data recorded at 12 weeks of follow up
Quality of Life (QOL) was assessed using the SF-36 (36-Item Short-Form Health Survey; QualityMetric, Lincoln, RI), MCS subscale. The SF-36 is a self-administered general health-related quality of life scale with 36 items. The MCS subscale has been shown to be responsive in psychoactive drug trials. The score range is 0-100. Higher scores represent better mental health; therefore, the least squares means listed here represent mean outcome changes from baseline.
Outcome measures
| Measure |
Guanfacine 0.1 mg
n=40 Participants
Guanfacine: Guanfacine 0.1 mg
|
Guanfacine 0.5 mg
n=39 Participants
Guanfacine: Guanfacine 0.5 mg
|
Placebo
n=40 Participants
Placebo: Placebo
|
|---|---|---|---|
|
Quality of Life (SF-36 MCS)
|
-0.618 units on a scale
Standard Error 0.825
|
-0.960 units on a scale
Standard Error 0.835
|
-0.083 units on a scale
Standard Error 0.829
|
Adverse Events
Guanfacine 0.1 mg
Serious events: 2 serious events
Other events: 25 other events
Deaths: 0 deaths
Guanfacine 0.5 mg
Serious events: 1 serious events
Other events: 32 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Guanfacine 0.1 mg
n=41 participants at risk
Guanfacine: Guanfacine 0.1 mg
|
Guanfacine 0.5 mg
n=41 participants at risk
Guanfacine: Guanfacine 0.5 mg
|
Placebo
n=41 participants at risk
Placebo: Placebo
|
|---|---|---|---|
|
Nervous system disorders
Speech impairment/Use of right side
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Infections and infestations
Pneumonia
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Blood and lymphatic system disorders
Hyponatremia
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Cardiac disorders
Non-ST Elevation Myocardial Infarction
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Nervous system disorders
Right Frontal Subarachnoid Hemorrhage
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
Other adverse events
| Measure |
Guanfacine 0.1 mg
n=41 participants at risk
Guanfacine: Guanfacine 0.1 mg
|
Guanfacine 0.5 mg
n=41 participants at risk
Guanfacine: Guanfacine 0.5 mg
|
Placebo
n=41 participants at risk
Placebo: Placebo
|
|---|---|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
2.4%
1/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Cardiac disorders
Chest Pain
|
0.00%
0/41
|
2.4%
1/41
|
2.4%
1/41
|
|
Cardiac disorders
Hypertension
|
2.4%
1/41
|
4.9%
2/41
|
0.00%
0/41
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Cardiac disorders
Palpitations
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Abrasion
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Skin and subcutaneous tissue disorders
Actinic Keratosis
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Bee Stings
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Skin and subcutaneous tissue disorders
Blister
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Bruising
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Hair Loss
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Skin and subcutaneous tissue disorders
Insect Bite
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Laceration
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Poison Ivy
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.4%
1/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Skin and subcutaneous tissue disorders
Shingles
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Skin and subcutaneous tissue disorders
Varicose Veins
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
General disorders
Cold Sores
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
General disorders
Dental Implants
|
0.00%
0/41
|
2.4%
1/41
|
2.4%
1/41
|
|
General disorders
Dry Mouth
|
7.3%
3/41
|
17.1%
7/41
|
0.00%
0/41
|
|
General disorders
Dry Socket
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
General disorders
Epistaxis
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Infections and infestations
Infection Post Tooth Extraction
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Ear and labyrinth disorders
Otitis Media
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Precancerous Lesion On Tongue
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
General disorders
Rhinorrhea
|
2.4%
1/41
|
0.00%
0/41
|
2.4%
1/41
|
|
General disorders
Sinus Congestion
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
General disorders
Sinusitis
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
General disorders
Sleep Apnea
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
General disorders
Sneezing
|
0.00%
0/41
|
4.9%
2/41
|
0.00%
0/41
|
|
General disorders
Sore Throat
|
2.4%
1/41
|
2.4%
1/41
|
0.00%
0/41
|
|
General disorders
Throat Swelling
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
General disorders
Tooth Abscess
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Blood and lymphatic system disorders
Hyponatremia
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Gastrointestinal disorders
Abdominal Cramps
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/41
|
2.4%
1/41
|
2.4%
1/41
|
|
Gastrointestinal disorders
Anorexia
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Gastrointestinal disorders
Constipation
|
7.3%
3/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Gastrointestinal disorders
Diarrhea
|
4.9%
2/41
|
4.9%
2/41
|
0.00%
0/41
|
|
Gastrointestinal disorders
Difficulty Swallowing
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Gastrointestinal disorders
Diverticulitis
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Gastrointestinal disorders
Gastroenteritis
|
0.00%
0/41
|
0.00%
0/41
|
9.8%
4/41
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Gastrointestinal disorders
Inguinal Hernia
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Gastrointestinal disorders
Irregular Bowl Movements
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Gastrointestinal disorders
Nausea
|
4.9%
2/41
|
2.4%
1/41
|
2.4%
1/41
|
|
General disorders
Allergies
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
General disorders
Diaphoresis
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
General disorders
Fall
|
4.9%
2/41
|
7.3%
3/41
|
2.4%
1/41
|
|
General disorders
Fever
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
General disorders
Night Sweats
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Renal and urinary disorders
Difficuluty Urinating
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Reproductive system and breast disorders
Diminished Libido
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Renal and urinary disorders
Urinary Frequency
|
0.00%
0/41
|
4.9%
2/41
|
0.00%
0/41
|
|
Reproductive system and breast disorders
Uterine Polyp
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
2.4%
1/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
Joint Pain
|
2.4%
1/41
|
9.8%
4/41
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
Leg Cramps
|
0.00%
0/41
|
0.00%
0/41
|
4.9%
2/41
|
|
Musculoskeletal and connective tissue disorders
Leg Pain
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasm
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Muscle Strain
|
0.00%
0/41
|
2.4%
1/41
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Sciatica
|
2.4%
1/41
|
2.4%
1/41
|
4.9%
2/41
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
2.4%
1/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Nervous system disorders
Cognitive Worsening
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Nervous system disorders
Fatigue
|
7.3%
3/41
|
17.1%
7/41
|
7.3%
3/41
|
|
Nervous system disorders
Headache
|
4.9%
2/41
|
4.9%
2/41
|
2.4%
1/41
|
|
Nervous system disorders
Insomnia
|
2.4%
1/41
|
4.9%
2/41
|
2.4%
1/41
|
|
Nervous system disorders
Ischemic Stroke
|
4.9%
2/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Nervous system disorders
Lightheadedness
|
0.00%
0/41
|
9.8%
4/41
|
9.8%
4/41
|
|
Nervous system disorders
Sedation
|
7.3%
3/41
|
2.4%
1/41
|
2.4%
1/41
|
|
Nervous system disorders
Subarachnoid Hemorrhage
|
0.00%
0/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Nervous system disorders
Syncope
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Nervous system disorders
Vertigo
|
2.4%
1/41
|
0.00%
0/41
|
2.4%
1/41
|
|
Eye disorders
Cataracts
|
4.9%
2/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Eye disorders
Sty
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Eye disorders
Subconjunctival Hemorrhage
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Eye disorders
Worsening in Near Vision
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Psychiatric disorders
Anxiety
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Psychiatric disorders
Irritability
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Psychiatric disorders
Sadness
|
2.4%
1/41
|
0.00%
0/41
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
0.00%
0/41
|
4.9%
2/41
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.9%
2/41
|
2.4%
1/41
|
4.9%
2/41
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
0.00%
0/41
|
2.4%
1/41
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
|
9.8%
4/41
|
7.3%
3/41
|
22.0%
9/41
|
|
Renal and urinary disorders
Urinary Tract Infection
|
2.4%
1/41
|
2.4%
1/41
|
7.3%
3/41
|
|
Musculoskeletal and connective tissue disorders
Low Back Pain
|
0.00%
0/41
|
0.00%
0/41
|
7.3%
3/41
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place