Anemia, Sickle Cell, Nocturnal Enuresis
Conditions
Brief summary
This study assesses if using the medication desmopressin will decrease nightime bedwetting in children with sickle cell disease.
Detailed description
Night time bedwetting is a common complication of sickle cell disease, and affects up to 30 % of children. Desmopressin is an oral medication that increases water reabsorption in the kidneys. Studies have shown that it is effective in decreasing bedwetting episodes in children without sickle cell disease. Chronic sickling episodes causing damage to the kidneys could cause permanent damage and may make this treatment ineffective in sickle cell disease. This trial will inform pediatric sickle cell doctors if desmopressin is an appropriate treatment for bed wetting in the investigators patients. This study expanded upon a previously terminated study which had separately registered (NCT02636387, ID: 2014-3768).
Interventions
DRUGDesmopressin
Two desmopressin 0.2 mg tablets at bedtime for 14 days and monitoring if \<50 % improvement
Sponsors
Montefiore Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with Hemoglobin SS, SC, SB0thal or SB+thal 2. Patients with at least two episodes of primary nocturnal enuresis per week or four episodes over the two weeks prior to enrollment. 3. Patients with secondary enuresis who have been evaluated and cleared by a pediatric urologist as not having other etiologies of enuresis (e.g. overactive detrusor activity, a genitourinary anatomic abnormality)
Exclusion criteria
1. Patients with developmental delay or neurologic dysfunction secondary to stroke. 2. Patients with hypertension or underlying renal disease. 3. Patients with genitourinary anatomic abnormalities. Any prior renal ultrasound showing normal genitourinary anatomy is sufficient to clear a patient for the study. 4. Patients with daytime urinary incontinence 5. Patients with glucosuria on urinalysis. 6. Patients with secondary nocturnal enuresis who have not been evaluated by a pediatric urologist to rule out other etiologies of enuresis. 7. Patients who are pregnant. 8. Patients receiving another medicine for nocturnal enuresis (e.g. imipramine).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bedwetting Episodes | Baseline and ~1 month | Change in the percentage of nights with bedwetting episodes assessed at baseline based on participant recall over the previous 14 nights, as well as at \ 1 month (30 nights) based on completion of a study (enuresis) diary. This is used to assess whether the use of desmopressin in patients with sickle cell disease and nocturnal enuresis will decrease the number of nighttime episodes of enuresis by 50% after initiating DDAVP at 0.4 mg nightly dose (with dose escalation as clinically appropriate). A negative value indicates a decrease in bedwetting episodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Bedwetting on Day to Day Activities | Baseline and 4 weeks | To determine if patients with sickle cell disease and nocturnal enuresis receiving desmopressin will have an improved quality of life compared to their baseline. This will be measured using the PedsQL Measurement Model which measures health related quality of life in children with acute and chronic health conditions, like sickle cell. The scales focuses on areas such as activities, feelings, and school performance. |
| Change in Nighttime Awakenings | Baseline and ~1 month | Change in the percentage of nights with awakenings over the previous 14 nights was assessed by summarizing and comparing baseline and 1 month nighttime awakening data. The percentage of nights with nighttime awakenings was evaluated at baseline based on recall and at 1 month (30 nights) based on completion of a study diary. This was used to determine whether the use of desmopressin in patients with sickle cell disease and nocturnal enuresis changes the rates of nighttime awakenings to urinate (nocturia), defined as episodes of nighttime awakening to void in children ≥5 years of age, compared to prior to initiating treatment with DDAVP. A positive value indicates an increase in nighttime awakenings |
| Change in Daytime Fatigue | Baseline and ~1 month | Change in daytime fatigue will be assessed to determine if patients with sickle cell disease and nocturnal enuresis receiving desmopressin will have less daytime fatigue compared to their baseline data. The PROMIS Pediatric Fatigue Short Form (Version 2.0) will be used to compare levels of fatigue from baseline and \ 1 month (30 nights) on the study medication. The PROMIS Fatigue scale, which utilizes a 7-day recall period, is a 10-item questionnaire consisting of 5 responses ranging from 1-5 with one indicative of Never and five indicative of almost always resulting in a raw scoring range of 10-50. Negative PROMIS change scores are associated with decreased levels of fatigue. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Desmopressin 0.2mg tablets, dose titrated to effect
NOTE: While an option, doses were not titrated for any of the participants in this study prior to study termination.
Desmopressin: Two desmopressin 0.2 mg tablets at bedtime for 14 days and monitoring if \<50 % improvement | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Never initiated medication | 2 |
Baseline characteristics
| Characteristic | Treatment Group |
|---|---|
| Age, Continuous | 12.1 years STANDARD_DEVIATION 2.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Genotype of Sickle Cell Disease Sickle Cell Anemia (Hb SS) | 6 Participants |
| Genotype of Sickle Cell Disease Sickle Hemoglobin-C Disease (Hb SC) | 2 Participants |
| Number of Bedwetting Days Based on Disease Type Sickle Cell Anemia (Hb SS) | 10.5 days STANDARD_DEVIATION 4 |
| Number of Bedwetting Days Based on Disease Type Sickle Hemoglobin-C Disease (Hb SC) | 8.5 days STANDARD_DEVIATION 0.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Change in Bedwetting Episodes
Change in the percentage of nights with bedwetting episodes assessed at baseline based on participant recall over the previous 14 nights, as well as at \ 1 month (30 nights) based on completion of a study (enuresis) diary. This is used to assess whether the use of desmopressin in patients with sickle cell disease and nocturnal enuresis will decrease the number of nighttime episodes of enuresis by 50% after initiating DDAVP at 0.4 mg nightly dose (with dose escalation as clinically appropriate). A negative value indicates a decrease in bedwetting episodes.
Time frame: Baseline and ~1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change in Bedwetting Episodes | -41 percentage of nights | Standard Deviation 26.2 |
Secondary
Change in Daytime Fatigue
Change in daytime fatigue will be assessed to determine if patients with sickle cell disease and nocturnal enuresis receiving desmopressin will have less daytime fatigue compared to their baseline data. The PROMIS Pediatric Fatigue Short Form (Version 2.0) will be used to compare levels of fatigue from baseline and \ 1 month (30 nights) on the study medication. The PROMIS Fatigue scale, which utilizes a 7-day recall period, is a 10-item questionnaire consisting of 5 responses ranging from 1-5 with one indicative of Never and five indicative of almost always resulting in a raw scoring range of 10-50. Negative PROMIS change scores are associated with decreased levels of fatigue.
Time frame: Baseline and ~1 month
Population: 1 month fatigue data was not able to collected from one participant who did not complete the 1 month PROMIS Fatigue questionnaire. Accordingly, change results were not available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group | Change in Daytime Fatigue | -6.0 score on a scale |
Secondary
Change in Nighttime Awakenings
Change in the percentage of nights with awakenings over the previous 14 nights was assessed by summarizing and comparing baseline and 1 month nighttime awakening data. The percentage of nights with nighttime awakenings was evaluated at baseline based on recall and at 1 month (30 nights) based on completion of a study diary. This was used to determine whether the use of desmopressin in patients with sickle cell disease and nocturnal enuresis changes the rates of nighttime awakenings to urinate (nocturia), defined as episodes of nighttime awakening to void in children ≥5 years of age, compared to prior to initiating treatment with DDAVP. A positive value indicates an increase in nighttime awakenings
Time frame: Baseline and ~1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Change in Nighttime Awakenings | 16.8 percentage of nights | Standard Deviation 25.3 |
Secondary
Impact of Bedwetting on Day to Day Activities
To determine if patients with sickle cell disease and nocturnal enuresis receiving desmopressin will have an improved quality of life compared to their baseline. This will be measured using the PedsQL Measurement Model which measures health related quality of life in children with acute and chronic health conditions, like sickle cell. The scales focuses on areas such as activities, feelings, and school performance.
Time frame: Baseline and 4 weeks
Population: Data was not collected for the Impact of Bedwetting on day-to-day activities.