ACE: The Effect of Anticholinergics on Cognitive Function in the Elderly

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT01922115
• Collaborator: American Urogynecologic Society (Other)
• Enrollment: 59
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Anticholinergic medication is used to treat overactive bladder (OAB). A known side effect of this medication is cognitive dysfunction. OAB is more prevalent in the elderly population - a group that also has a higher baseline risk of cognitive dysfunction. Our objective is to evaluate the effect of an anticholinergic medication on cognitive function in elderly women.

Condition or Disease	Intervention/Treatment	Phase
Mental Competency; Urinary Bladder, Overactive; Cognitive Function	Drug: Trospium Chloride; Drug: Placebo	Phase 4

Detailed Description

Subjects will be randomized to: 1) trospium chloride or 2) placebo.

There are three aims:

1. To evaluate changes in cognitive function in elderly women taking trospium versus placebo, using validated cognitive assessment tests

2. To develop a useful battery of cognitive screening tests for monitoring the cognitive safety of OAB management

3. To understand how the timing of cognitive changes relates to the timing of improvement in OAB symptoms. The investigators will recruit 60 women aged ≥ 50 with the diagnosis of OAB. Cognitive assessments will be performed at baseline and Week 1 and 4 after drug initiation using paper-based validated questionnaires. OAB improvement will be assessed with validated questionnaires.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: The Effect of Anticholinergics on Cognitive Function in the Elderly: a Randomized Controlled Trial
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: TROSPIUM CHLORIDE Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg).	Drug: Trospium Chloride; Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.; Other Names: Sanctura XR
Placebo Comparator: PLACEBO Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride).	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Hopkins Verbal Learning Test - Revised [Week 4]

   Assesses short term verbal learning and memory. Subscales include immediate recall (0-36) and delayed recall (0-12). Higher values indicate better outcomes.

2. Hopkins Verbal Learning Test - Revised [Week 4]

   Assesses short term verbal learning and memory. See below for the subscale delayed recognition (0-24). Percentages of total responses correct are reported for delayed recognition, higher values indicate better outcomes.

Secondary Outcome Measures

1. Mini-Mental State Examination [Week 4]

   The mini-mental state examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia. The range is 0-30, with higher values indicating better outcomes.

2. Overactive Bladder Questionnaire [Week 4]

   The Overactive Bladder Questionnaire (OAB-q) was developed to assess symptom bother and the impact of overactive bladder (OAB) on health-related quality of life (HRQL). The instrument was developed and validated in both continent and incontinent OAB patients, including both men and women. Total range is 19-101 and higher values indicate worse outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 99 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Female 50 or older

• Diagnosis of OAB (ICS definition)

• English literacy

• Ability to swallow oral medication

• Cognitive ability to give consent

Exclusion Criteria:

• Dementia/Depression/Delirium

• Current anticholinergic use (requires 2 week washout period)

• Current cholinesterase

• Urinary or gastric retention

• Severe decreased gastrointestinal motility

• Uncontrolled narrow-angle glaucoma

• Myasthenia gravis

• Diagnosis fo renal impairment (creatinine clearance <30 mL/min)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Unc Chapel Hill Urogynecology A2 Clinic	Chapel Hill	North Carolina	United States	27517

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• American Urogynecologic Society

Investigators

• Principal Investigator: Elizabeth Geller, MD, UNC CHAPEL HILL

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT01922115
• Other Study ID Numbers: 13-1352
• First Posted: Aug 14, 2013
• Last Update Posted: Mar 22, 2017
• Last Verified: Feb 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of North Carolina, Chapel Hill: COGNITIVE FUNCTION; OVERACTIVE BLADDER; [C23.888.942.343.780]
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Trospium chloride

Study Results

Participant Flow

Arm/Group Title	TROSPIUM CHLORIDE	PLACEBO
Arm/Group Description	Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg). Trospium Chloride: Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.	Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride). Placebo
Period Title: Overall Study
STARTED	28	31
COMPLETED	21	24
NOT COMPLETED	7	7

Baseline Characteristics

Arm/Group Title	TROSPIUM CHLORIDE	PLACEBO	Total
Arm/Group Description	Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg). Trospium Chloride: Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.	Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride). Placebo	Total of all reporting groups
Overall Participants	28	31	59
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.39 (11.615)	68.71 (10.615)	68.56 (11.005)
Sex: Female, Male (Count of Participants)
Female	28 100%	31 100%	59 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	7 25%	25 80.6%	32 54.2%
Black	21 75%	4 12.9%	25 42.4%
Hispanic	0 0%	1 3.2%	1 1.7%
Asian	0 0%	1 3.2%	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Hopkins Verbal Learning Test - Revised
Description	Assesses short term verbal learning and memory. Subscales include immediate recall (0-36) and delayed recall (0-12). Higher values indicate better outcomes.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TROSPIUM CHLORIDE	PLACEBO
Arm/Group Description	Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg). Trospium Chloride: Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.	Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride). Placebo
Measure Participants	21	24
Immediate Recall	22.00 (5.51)	24.38 (5.96)
Delayed Recall	6.71 (2.80)	7.83 (3.28)

2. Secondary Outcome

Title	Mini-Mental State Examination
Description	The mini-mental state examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia. The range is 0-30, with higher values indicating better outcomes.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TROSPIUM CHLORIDE	PLACEBO
Arm/Group Description	Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg). Trospium Chloride: Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.	Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride). Placebo
Measure Participants	21	24
Mean (Standard Deviation) [units on a scale]	28.14 (1.90)	28.38 (1.76)

3. Secondary Outcome

Title	Overactive Bladder Questionnaire
Description	The Overactive Bladder Questionnaire (OAB-q) was developed to assess symptom bother and the impact of overactive bladder (OAB) on health-related quality of life (HRQL). The instrument was developed and validated in both continent and incontinent OAB patients, including both men and women. Total range is 19-101 and higher values indicate worse outcomes.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TROSPIUM CHLORIDE	PLACEBO
Arm/Group Description	Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg). Trospium Chloride: Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.	Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride). Placebo
Measure Participants	21	24
Mean (Standard Deviation) [units on a scale]	41.45 (18.84)	56.04 (20.21)

4. Primary Outcome

Title	Hopkins Verbal Learning Test - Revised
Description	Assesses short term verbal learning and memory. See below for the subscale delayed recognition (0-24). Percentages of total responses correct are reported for delayed recognition, higher values indicate better outcomes.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TROSPIUM CHLORIDE	PLACEBO
Arm/Group Description	Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg). Trospium Chloride: Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.	Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride). Placebo
Measure Participants	21	24
Mean (Standard Deviation) [percentage of total correct]	81.68 (47.45)	83.49 (26.72)

Adverse Events

Arm/Group Title	TROSPIUM CHLORIDE		PLACEBO
Arm/Group Description	Those with overactive bladder will be administered either a placebo or Sanctura XR extended release (Trospium chloride) for treatment (60 mg). Trospium Chloride: Subject will be administered either placebo or 60 mg dosage of Sanctura XR for treatment of overactive bladder. Subject will take Sanctura XR once every morning. Blood will be drawn for plasma extraction at each visit.		Subjects may be administered a placebo rather than the Sanctura XR (Trospium Chloride). Placebo
All Cause Mortality
	TROSPIUM CHLORIDE		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TROSPIUM CHLORIDE		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/28 (7.1%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Distress	1/28 (3.6%)	1	0/31 (0%)	0
Vascular disorders
Blood Clot	1/28 (3.6%)	1	0/31 (0%)	0
Other (Not Including Serious) Adverse Events
	TROSPIUM CHLORIDE		PLACEBO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/28 (35.7%)		2/31 (6.5%)
Eye disorders
Dry Eyes	0/28 (0%)	0	1/31 (3.2%)	1
Gastrointestinal disorders
Constipation	4/28 (14.3%)	4	1/31 (3.2%)	1
Dry Mouth	4/28 (14.3%)	4	0/31 (0%)	0
General disorders
Dizziness	1/28 (3.6%)	1	0/31 (0%)	0
Psychiatric disorders
Depression	1/28 (3.6%)	1	0/31 (0%)	0
Mood Swings	0/28 (0%)	0	1/31 (3.2%)	1
Renal and urinary disorders
UTI	1/28 (3.6%)	1	0/31 (0%)	0
Skin and subcutaneous tissue disorders
Skin Rash	1/28 (3.6%)	1	0/31 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.