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

A Parallel, Double-blind Comparison of Tolterodine vs. Placebo Treatments for Nocturia in Postmenopausal Women.

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.

Study Overview

• Status: Terminated
• Conditions: Urinary Incontinence
• Intervention / Treatment: Drug: tolterodine

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 Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02120
      • Brigham & Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nocturnal Urinary Frequency, Recorded on an Event/Symptom Chart;	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 months
Urgency	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;
Number of Incontinence Episodes;	Number	Duration of Study
Relationship of Incontinence to Urge or Stress	4-grade scale	Duration of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychological Self-reports, Scores on Anxiety and Depression Rating Scales;	State and Trait scores on Spielberger State-Trait Anxiety Inventory; The score measured by the Zung Self-Rating Depression Inventory.	2 weeks
Quality of Life, Scores on the Women's Health Questionnaire.	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.	2 weeks
Sleep Quality		2 months
Cognitive Function	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)	Two 20-minute sessions during 2 months
Hyperarousal	Score on 26-item self-report Hyperarousal Scale that indicates proportion of attention allocated to visceral-somatic information vs. external sensory data.	At baseline and 8 weeks later
Whether She Used Any Pads.	Yes/No	Duration of Study
Pads Used	Pads used	Duration of Study

Other Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General 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. doi: 10.1093/sleep/26.3.342.
• Roehrs T, Merlotti L, Petrucelli N, Stepanski E, Roth T. Experimental sleep fragmentation. Sleep. 1994 Aug;17(5):438-43. doi: 10.1093/sleep/17.5.438.
• Shaver JL, Paulsen VM. Sleep, psychological distress, and somatic symptoms in perimenopausal women. Fam Pract Res J. 1993 Dec;13(4):373-84.
• 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. doi: 10.1093/sleep/16.2.151.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: May 5, 2006
• First Submitted That Met QC Criteria: May 5, 2006
• First Posted (Estimate): May 9, 2006

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: sleep; menopause; overactive bladder; sleep disorder; urinary incontinence; nocturia; tolterodine; midlife women; psychological tests
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Urination Disorders; Elimination Disorders; Urinary Incontinence; Enuresis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Tolterodine Tartrate
• Other Study ID Numbers: 2005-P-000960