A Comparison of Tolterodine and Placebo Treatments on Nocturnal Frequency and Sleep Quality in Women After Menopause.

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00323635
• Collaborator: Pfizer (Industry)
• Enrollment: 19
• Locations: 2
• Arms: 2
• Duration (Months): 57
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is being done to compare frequency of urination during the night when women take tolterodine tablets vs. when they take placebo tablets.

We will also measure whether between these two treatment conditions there are any differences in women's sleep, mood and performance on cognitive tests.

Condition or Disease	Intervention/Treatment	Phase
Urinary Incontinence	Drug: tolterodine	Phase 4

Detailed Description

From midlife onwards, about half of women complain of poor sleep quality. One possible reason might be an increased frequency of need to urinate during the night. Women feel more frequent urges to urinate when structures that support the bladder become more lax. Tolterodine is a drug that can raise the threshold for volume of urine that accumulates in the bladder before the urge to urinate arises.

Many factors determine how people say they sleep, such as their sleep as recorded by sleep-measuring instruments, how closely they notice their night's sleep, whether they are generally prone to make positive or negative judgments or to have a lot or a few body symptoms.

In this study, women between ages 45 to 65 who are past the menopause and who are frequently bothered by the need to urinate during the night will take either tolterodine or placebo tablets for 8 weeks. During the last week they will record the hours they slept and the quality of their sleep each morning. They will wear a device on their wrist through the week that continuously records whether they are asleep or awake. During three nights of the week they will record the volume of urine whenever they urinate. At the end of the week they will complete questionnaires about their mood and take some computerized tests that measure their alertness. Thereafter they will repeat these procedures, taking the kind of tablets they did not take during the first 8-week treatment period.

We will compare the frequency of urination, sleep, mood as adjusted for the tendency to make positive or negative judgments and daytime attention level to find if any of these differ between the two treatment periods, and to explain differences between any differences that may be found.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Parallel, Double-blind Comparison of Tolterodine vs. Placebo Treatments for Nocturia in Postmenopausal Women.
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tolterodine Tolterodine 4 mg q.d. X 8 weeks	Drug: tolterodine; tablet, 4 mg, daily, 1 month; Other Names: Detrol
Placebo Comparator: Placebo A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine	Drug: tolterodine; tablet, 4 mg, daily, 1 month; Other Names: Detrol

Outcome Measures

Primary Outcome Measures

1. Nocturnal Urinary Frequency, Recorded on an Event/Symptom Chart; [2 months]

   Subjects note: 1. Number of nocturnal and diurnal voids; 2) level of urgency for 7 days, graded 1 to 4, beginning after the first void on the Friday morning of week 7 and week 13 of their participation; 3) Number of incontinence episodes; 4) Relationship of incontinence to urge or stress (4 grade scale); 4) Whether she used any pads.

2. Urgency [Beginning after the first void on the Friday morning of week 7 and week 13 of their participation;]

   Level of urgency for 7 days, graded 1 to 4,

3. Number of Incontinence Episodes; [Duration of Study]

   Number

4. Relationship of Incontinence to Urge or Stress [Duration of study]

   4-grade scale

Secondary Outcome Measures

1. Psychological Self-reports, Scores on Anxiety and Depression Rating Scales; [2 weeks]

   State and Trait scores on Spielberger State-Trait Anxiety Inventory; The score measured by the Zung Self-Rating Depression Inventory.

2. Quality of Life, Scores on the Women's Health Questionnaire. [2 weeks]

   Self-reported vasomotor symptoms, other somatic symptoms, anxiety, depression, sleep and cognitive symptoms (memory, concentration and clumsiness problems), measured as category scores. Subjective sleep onset and total sleep times measured as 7-day averaged minutes.

3. Sleep Quality [2 months]

4. Cognitive Function [Two 20-minute sessions during 2 months]

   Motor speed (number of finger taps in 30 seconds); Continuous Performance (mean response time elicited by appearance of target alphabet letter presented in a series of letters on a monitor screen for 1 minute); Color-Word Stroop Test (response times to stimuli with congruent word and color)

5. Hyperarousal [At baseline and 8 weeks later]

   Score on 26-item self-report Hyperarousal Scale that indicates proportion of attention allocated to visceral-somatic information vs. external sensory data.

6. Whether She Used Any Pads. [Duration of Study]

   Yes/No

7. Pads Used [Duration of Study]

   Pads used

Other Outcome Measures

1. Sleep / Wake Pattern [Two weeks]

   Wrist actigraphy measures of total daytime and nighttime activity scored by standardized Actiwatch measures of sleep and sake.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Post-menopausal women, age 45 to 65 years old.

2. No menses for at least 6 months before the study start.

3. Have at least 14 episodes of nocturia per week.

4. Have at least 4 hot flashes daily.

5. Overall good health, as evidenced by a letter from the primary care provider.

6. Agree not to use exogenous hormones including soy isoflavones or soybean-based shakes, or nutritional supplements that potentially reduce hot flashes.

7. Have discontinued all hormone treatments, systemic, topical, or vaginal, at least 60 days before admission and throughout participation in the study.

Exclusion Criteria:

1. Use of anti-cholinergic, hypnotic or sedating drugs

2. Presence of urinary retention, gastric retention, chronic severe constipation,or narrow-angled glaucoma.

3. A urinary tract infection within a month of study start.

4. Undiagnosed abnormal vaginal bleeding.

5. Benign or malignant liver disease.

6. History or presence of chronic alcoholism or medication addiction within the past 5 yrs.

7. An acute systemic infection within seven days before the study start.

8. Concurrent participation in another clinical trial and/or receiving an experimental medication/device in the last 30 days before admission to the study.

9. History of shift work within the past 6 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Brigham & Women's Hospital	Boston	Massachusetts	United States	02120

Sponsors and Collaborators

• Brigham and Women's Hospital
• Pfizer

Investigators

• Principal Investigator: Quentin R Regestein, M.D., Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ancoli-Israel S, Cole R, Alessi C, Chambers M, Moorcroft W, Pollak CP. The role of actigraphy in the study of sleep and circadian rhythms. Sleep. 2003 May 1;26(3):342-92. Review.
• Brooks JO 3rd, Friedman L, Bliwise DL, Yesavage JA. Use of the wrist actigraph to study insomnia in older adults. Sleep. 1993 Feb;16(2):151-5.
• Roehrs T, Merlotti L, Petrucelli N, Stepanski E, Roth T. Experimental sleep fragmentation. Sleep. 1994 Aug;17(5):438-43.
• Shaver JL, Paulsen VM. Sleep, psychological distress, and somatic symptoms in perimenopausal women. Fam Pract Res J. 1993 Dec;13(4):373-84.

• Responsible Party: Quentin Rodney Regestein, MD, Physician, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00323635
• Other Study ID Numbers: 2005-P-000960
• First Posted: May 9, 2006
• Last Update Posted: Mar 29, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Quentin Rodney Regestein, MD, Physician, Brigham and Women's Hospital: nocturia; urinary incontinence; overactive bladder; tolterodine; sleep; sleep disorder; menopause; midlife women; psychological tests
• Additional relevant MeSH terms: Urinary Incontinence; Enuresis; Tolterodine Tartrate

Study Results

Participant Flow

Recruitment Details	Women 45 to 65 years old were mailed post-cards with the study telephone number and e-mail address. Subjects were assessed for eligibility. The PI determined eligibility based on the study criteria. Eligible subjects were informed about the study requirements, risks and benefits, and then required to read and sign a consent form.
Pre-assignment Detail	Placebo responders were excluded after one week.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
Period Title: Overall Study
STARTED	10	9
COMPLETED	10	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Tolterodine	Placebo	Total
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine	Total of all reporting groups
Overall Participants	10	9	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	9 100%	19 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (5.2)	53 (5.2)	52 (5.2)
Sex: Female, Male (Count of Participants)
Female	10 100%	9 100%	19 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	9 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Nocturnal Urinary Frequency, Recorded on an Event/Symptom Chart;
Description	Subjects note: 1. Number of nocturnal and diurnal voids; 2) level of urgency for 7 days, graded 1 to 4, beginning after the first void on the Friday morning of week 7 and week 13 of their participation; 3) Number of incontinence episodes; 4) Relationship of incontinence to urge or stress (4 grade scale); 4) Whether she used any pads.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
Measure Participants	0	0

2. Primary Outcome

Title	Urgency
Description	Level of urgency for 7 days, graded 1 to 4,
Time Frame	Beginning after the first void on the Friday morning of week 7 and week 13 of their participation;

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
Measure Participants	0	0

3. Primary Outcome

Title	Number of Incontinence Episodes;
Description	Number
Time Frame	Duration of Study

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
Measure Participants	0	0

4. Primary Outcome

Title	Relationship of Incontinence to Urge or Stress
Description	4-grade scale
Time Frame	Duration of study

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
Measure Participants	0	0

5. Secondary Outcome

Title	Psychological Self-reports, Scores on Anxiety and Depression Rating Scales;
Description	State and Trait scores on Spielberger State-Trait Anxiety Inventory; The score measured by the Zung Self-Rating Depression Inventory.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks tolterodine: tablet, 4 mg, daily, 1 month	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine tolterodine: tablet, 4 mg, daily, 1 month
Measure Participants	0	0

6. Secondary Outcome

Title	Quality of Life, Scores on the Women's Health Questionnaire.
Description	Self-reported vasomotor symptoms, other somatic symptoms, anxiety, depression, sleep and cognitive symptoms (memory, concentration and clumsiness problems), measured as category scores. Subjective sleep onset and total sleep times measured as 7-day averaged minutes.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks tolterodine: tablet, 4 mg, daily, 1 month	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine tolterodine: tablet, 4 mg, daily, 1 month
Measure Participants	0	0

7. Secondary Outcome

Title	Sleep Quality
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks tolterodine: tablet, 4 mg, daily, 1 month	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine tolterodine: tablet, 4 mg, daily, 1 month
Measure Participants	0	0

8. Secondary Outcome

Title	Cognitive Function
Description	Motor speed (number of finger taps in 30 seconds); Continuous Performance (mean response time elicited by appearance of target alphabet letter presented in a series of letters on a monitor screen for 1 minute); Color-Word Stroop Test (response times to stimuli with congruent word and color)
Time Frame	Two 20-minute sessions during 2 months

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks tolterodine: tablet, 4 mg, daily, 1 month	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine tolterodine: tablet, 4 mg, daily, 1 month
Measure Participants	0	0

9. Secondary Outcome

Title	Hyperarousal
Description	Score on 26-item self-report Hyperarousal Scale that indicates proportion of attention allocated to visceral-somatic information vs. external sensory data.
Time Frame	At baseline and 8 weeks later

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks tolterodine: tablet, 4 mg, daily, 1 month	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine tolterodine: tablet, 4 mg, daily, 1 month
Measure Participants	0	0

10. Secondary Outcome

Title	Whether She Used Any Pads.
Description	Yes/No
Time Frame	Duration of Study

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
Measure Participants	0	0

11. Secondary Outcome

Title	Pads Used
Description	Pads used
Time Frame	Duration of Study

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
Measure Participants	0	0

12. Other Pre-specified Outcome

Title	Sleep / Wake Pattern
Description	Wrist actigraphy measures of total daytime and nighttime activity scored by standardized Actiwatch measures of sleep and sake.
Time Frame	Two weeks

Outcome Measure Data

Analysis Population Description

No data collected or analyzed for the outcome measures.

Arm/Group Title	Tolterodine	Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks tolterodine: tablet, 4 mg, daily, 1 month	A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine tolterodine: tablet, 4 mg, daily, 1 month
Measure Participants	0	0

Adverse Events

Time Frame	9 weeks
Adverse Event Reporting Description	Only serious adverse effects were collected
Arm/Group Title	Tolterodine		Placebo
Arm/Group Description	Tolterodine 4 mg q.d. X 8 weeks		A capsule of identical to tolterodine in taste, smell and appearance that contains no tolterodine
All Cause Mortality
	Tolterodine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tolterodine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/10 (0%)	0	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Tolterodine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.