Hyponatremia, Inappropriate ADH Syndrome
Conditions
Keywords
Hyponatremia, SIADH, SIAD, Urea
Brief summary
This study is examining how a dietary supplement called urea can be used to treat low blood sodium level. Low blood sodium level is a common problem and some studies show that many patients with low blood sodium level suffer from brain fog and/or loss of balance. Unfortunately, it is unknown at this point what the best treatment is for low blood sodium level. With this pilot research study, the investigators are hoping to learn more about whether urea is safe to take, whether patients can tolerate taking urea for several weeks, whether urea increases blood sodium level, and whether urea can help prevent the brain fog and/or loss of balance that some patients with low blood sodium level suffer from. The information obtained with this study is intended to be used to design a larger study in the future to get a definite answer whether urea is beneficial for patients with low blood sodium level.
Detailed description
Hyponatremia is the most common electrolyte disorder encountered clinically. While acute and/or severe hyponatremia is commonly associated with significant symptoms, milder and more chronic forms of hyponatremia remain clinically inconspicuous as the brain effectively adapts to the low extracellular osmolality. However, recent evidence suggests that even mild hyponatremia is associated with subtle neurocognitive deficits, gait disturbances, falls, fractures, and osteoporosis, as well as increased mortality. Current therapeutic interventions for hyponatremia, including fluid restriction and loop diuretics lack clinical trial data to support their efficacy and are commonly associated with poor adherence. The discovery of vasopressin antagonists (vaptans) provided a new drug class targeting the most common mechanism of hyponatremia, i.e., elevated vasopressin. Despite the demonstrated efficacy of vaptans in clinical trials, their use has been limited by high cost as well as safety concerns related to risk of liver injury and the potential for rapid correction of hyponatremia. Thus, despite the significant morbidity and mortality associated with chronic non-severe hyponatremia, there is a paucity of definitively effective, safe, well-tolerated, and reasonably priced treatments. Small European case series have suggested that oral urea is safe and effective for the treatment of hyponatremia. However, urea has not been available for the treatment of hyponatremia in the United States until very recently. This research group recently published the first and only study describing the effectiveness and safety of a new American formulation of oral urea among hospitalized patients with hyponatremia. However, the latter was a retrospective study limited to hospitalized patients. Data from large clinical trials on the efficacy of urea for the prevention of patient-centered outcomes in those with chronic hyponatremia are lacking. The current proposal is a pilot study that seeks to establish the feasibility of recruiting ambulatory patients with chronic hyponatremia into a study of urea, determine the acceptability of urea to patients, and explore the effect of this agent on plasma sodium level (PNa), neurocognitive function, and postural stability. The investigators will recruit 30 ambulatory patients with chronic non-severe hyponatremia and randomize them to oral urea or no drug treatment for a period of 42 days. Following this initial phase, all participants will have a 10-day washout period, followed by a 42-day period in which participants initially randomized to no drug therapy will receive urea and those initially treated with urea will receive no drug therapy. The investigators will collect data regarding the ease of recruitment, participant adherence to urea, and adverse events related to its use. The investigators will monitor participants' PNa, neurocognitive function, and postural stability over the course of the study. The feasibility, acceptability, and proof of concept/efficacy data from this pilot study will confirm the investigator's capacity to conduct, and will inform the design of a large clinical trial that will assess the efficacy of urea for the prevention of serious clinical outcomes of chronic non-severe hyponatremia.
Interventions
DRUGUrea
Groups On Urea, Then Off Urea and Off Urea, Then On Urea will receive urea during period 1 and period 2 of the study, respectively. The investigators will use the new American formulation of oral urea (i.e., Ure-Na™), which is packaged as a powder and mixed with 4 ounces. of water for oral consumption. Urea will be started at a dose of 15 grams of urea per mouth once daily. Dose titration will be based on the absolute increase in PNa on days 7 and 14. The urea dosing scheme will involve increasing from the starting dose of 15 grams/day to 30 grams/day (in 2 divided doses) based on the change in and absolute value of PNa, and subsequently, from 30 grams/day to 60 grams/day (in 2 divided doses) when indicated. The maximal dose of urea administered will be 60 g/day.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Helbert Rondon Berrios, MD, MS
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Attended ≥1 visit at a University of Pittsburgh Medical Center (UPMC) outpatient clinic within the prior 12 months * Chronic hyponatremia with a history of ≥ 2 sequential plasma sodium concentration (PNa) between 125 mmol/L and 132 mmol/L performed ≥ 14 days apart within the last 12 months with most recent PNa ≤ 132 mmol/L prior to screening * Patients are ambulatory without the need for any assist device (e.g., cane, walker) * Mini-mental state examination (MMSE) score ≥ 25 * Diagnosis of SIADH established by the Bartter and Schwartz criteria as follows: 1. Hyponatremia with a PNa between 125 mmol/L and 132 mmol/L 2. Plasma osmolality \< 275 mOsm/kg 3. Clinical euvolemia 4. Urine osmolality \> 100 mosm/kg 5. Urine Na ≥ 20 mmol/L 6. Intact adrenal function (i.e., morning plasma cortisol value ≥15 μg/dL, or negative corticotropin stimulation test) 7. Normal thyroid stimulating hormone (TSH) level (i.e., TSH between 0.3 to 5 μIU/mL) 8. eGFR \>= 45 ml/min/1.73 m2)
Exclusion criteria
* Cirrhosis and/or end-stage liver disease * Heart failure on diuretics and/or with recorded left ventricular ejection fraction \<40 percent * Chronic kidney disease with most recent estimated glomerular filtration rate \<45 ml/min/1.73m2 * Adrenal insufficiency * Untreated hypothyroidism * Urinary tract obstruction within the prior 2 months * Uncontrolled hyperglycemia (most recent random plasma glucose ≥ 200 mg/dL) * Ongoing drug treatment for hyponatremia with vaptans or combination of loop diuretics and salt tablets. * Active malignancy * Active infection * Neurological disorders with impairment of ambulation or cognition * End-stage lung disease with marked impairment in ambulatory capacity * Chronic pain with impairment of ambulation or cognition * Chronic nausea * Hypersensitivity to urea * Women who are pregnant, breast feeding, or of childbearing potential who are not using contraception * Patient is unable to consent for himself/herself
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Related to Urea | Baseline to day 42 while taking urea | To be assessed by medication side effect questionnaire. A tabulation of counts of participants experiencing specific known side effects of urea as well as their intensity (mild, moderate or severe) will be performed. |
| Change in Percentage Angular Deviation of Vestibular Control System Using Dynamic Representation of Upright Stance | Baseline to day 42 | Change in percentage angular deviation of vestibular control system using dynamic representation of upright stance from baseline to day 42. This was assessed using the NeuroCom™ Sensory Organization. This test enables both the examination of postural control and stability in response to a direct perturbation of the vestibular control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the vestibular system involved in maintaining upright stance in dynamic situations. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in vestibular balance control. |
| Change in Percentage Angular Deviation of Somatosensory Control System Using Dynamic Representation of Upright Stance | Baseline to day 42 | Change in percentage angular deviation of somatosensory control system using dynamic representation of upright stance from baseline to day 42. This will be assessed using the NeuroCom™ Sensory Organization. This test enables both the examination of postural control and stability in response to a direct perturbation of the somatosensory control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the somatosensory system involved in maintaining upright stance in dynamic situations. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in somatosensory balance control. |
| Change in Percentage Angular Deviation of Visual Control System Using Dynamic Representation of Upright Stance | Baseline to 42 days | Change in percentage angular deviation of visual control system using dynamic representation of upright stance from baseline to day 42. This will be assessed using the NeuroCom™ Sensory Organization. This test enables both the examination of postural control and stability in response to a direct perturbation of the visual control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the visual system involved in maintaining upright stance in dynamic situations. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in visual balance control. |
| Change in Percentage Weight Symmetry Using Dynamic Representation of Upright Stance | Baseline to day 42 | Change in percentage weight symmetry using dynamic representation of upright stance from baseline to day 42. This will be assessed using the Motor Control Test (MCT). MCT assesses the ability to quickly recover from an unexpected external translation. Weight symmetry indicates weight distribution under the left and right legs prior to perturbation onset. A score of 100 indicates perfect between-limb symmetry. Larger deviations away (higher or Lower) from 100 indicate asymmetry. Scores goes from -100 to +100 closer to 100 is optimal. |
| Change in Movement Latency of Posture Control and Stability Using Dynamic Representation of Upright Stance | Baseline to day 42 | Change in movement latency of posture control and stability using dynamic representation of upright stance from baseline to day 42. This will be assessed using the Motor Control Test (MCT). MCT assesses the ability to quickly recover from an unexpected external translation. Latency scores measure the time lapse between force plate translation on postural response for healthy, elderly populations, with previously reported mean latency values ranging from 126.80-131.40. Higher/Larger scores indicate poorer balance control. |
| Change in Amplitude Scaling of Posture Control and Stability Using Dynamic Representation of Upright Stance | Baseline to day 42 | Change in amplitude scaling of posture control and stability using dynamic representation of upright stance from baseline to day 42. This will be assessed using the Motor Control Test (MCT). MCT assesses the ability to quickly recover from an unexpected external translation. It is scored in units of angular momentum and normalized to body height and weight. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in ability to recover from an unexpected external translation reflecting better balance. |
| Number and Proportion of Participants Enrolled in the Study With Adverse Events Related to the Use of Urea | Baseline to day 42 while taking urea | Number and proportion of participants enrolled in the study with adverse events related to the use of urea from baseline to day 42. To be assessed by medication side effect questionnaire. |
| Number and Percentage of Participants Who Met Inclusion/Exclusion Criteria and Were Enrolled in the Study | 9 months | Number and percentage of participants who met inclusion/exclusion criteria and were enrolled in the study. To be assessed by analysis of enrollment data. |
| Number and Percentage of Participants Enrolled Who Completed the Study | 9 months | Number and percentage of participants enrolled who completed the study. To be assessed by analysis of enrollment and completion data. |
| Monthly Enrollment Rate | 9 months | Number of participants enrolled in the study every month. To be assessed by analysis of enrollment data |
| Number of Prescribed Urea Doses Taken by Participants | Baseline to day 42 while taking urea | Number of prescribed urea doses taken by participants. To be assessed by records in study diary and number of returned medication doses. |
| Reasons for Non-Adherence to Urea Therapy | Baseline to day 42 while taking urea | Reasons for non-adherence to urea therapy. To be assessed by medication acceptability and medication side effect questionnaires |
| Change in Plasma Sodium Concentration | Baseline to day 42 | Change in plasma sodium concentration from baseline to day 42. Based on plasma sodium assessments on days 0 and 42. |
| Change in Percentage Accuracy Action Boundary Selection | Baseline to day 42 | Change in percentage accuracy action boundary selection from baseline to day 42. This will be measured by the Perception-Action Coupling Task (PACT) which is an affordance-based assessment conducted on an iPad, which uses matched pairs of 'virtual' balls and 'virtual' holes to assess patients' ability to accurately assess their action boundaries. Accuracy of affordance perception is measured. Scores goes from 0% to 100% with higher score representing increased accuracy |
| Change in Overall Score of Sensorimotor Ability Battery | Baseline to day 42 | Change in overall score of sensorimotor ability battery from baseline to day 42. This will be measured by the Senaptec Sensory Station™ test battery which examines separate sensorimotor elements including; multiple object tracking, reaction time, perception span, go/no go, depth perception and dynamic visual acuity. Score goes from 0 to1500 with higher scores representing better sensorimotor ability |
| Change in the Sample Entropy of the Center of Pressure Data From the Force Plate | Baseline to day 42 | Measure the 'structure' of the noise in the oscillations of the center of mass of the individual. The measurement represent the percentage of displacement from the center of pressure. No reference ranges are available as these vary according to the population studied |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Patients Screened Who Met Inclusion/Exclusion Criteria for the Study | 9 months | Number and percentage of patients screened who met inclusion/exclusion criteria for the study. To be assessed by analysis of screening and enrollment data. |
| Number and Proportion of Participants Who Took More Than 80 Percent of Prescribed Urea Doses | Baseline to day 42 while taking urea | Number and proportion of participants who took more than 80 percent of prescribed urea doses. To be assessed by analysis of study diary and number of returned medication doses. |
| Number and Proportion of Participants Who Thought the Medication Was Acceptable | Baseline to day 42 while taking urea | Number and proportion of participants who thought the medication was acceptable. Based on ratings for acceptability in the medication acceptability questionnaire. |
| Average Ratings for Medication Acceptability | Baseline to day 42 while taking urea | Average ratings using a 5-point Likert scale medication acceptability questionnaire. in which responders specify their level of agreement to a statement in five points: (1) Strongly disagree; (2) Disagree; (3) Neutral; (4) Agree; (5) Strongly agree; or (1) Very Unhappy; (2) Unhappy; (3) Neutral; (4) Happy; (5) Very Happy. A higher overall score represents more acceptability |
| Change in SF-12 (Health Survey) Mental Component Summary (MCS) | Baseline to day 42 | Change in SF-12 (Health Survey) Mental Component Summary (MCS) from baseline to day 42. Based on SF-12 MCS assessments on days 0 and 42. This is computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
| Change in SF-12 (Health Survey) Physical Component Summary (PCS) | Baseline to day 42 | Change in SF-12 (Health Survey) Physical Component Summary (PCS) from baseline to day 42. Based on SF-12 PCS assessments on days 0 and 42. This is computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
| Number of Patients Screened | 9 months | Number of patients screened. To be assessed by analysis of screening data. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| On Urea, Then Off Urea Participants assigned to this group will receive oral urea for 42 days (period 1), followed by a 10-day washout period, and then will be off urea for 42 days (period 2).
Urea: Groups On Urea, Then Off Urea and Off Urea, Then On Urea will receive urea during period 1 and period 2 of the study, respectively. The investigators will use the new American formulation of oral urea (i.e., Ure-Na™), which is packaged as a powder and mixed with 4 ounces. of water for oral consumption. Urea will be started at a dose of 15 grams of urea per mouth once daily. Dose titration will be based on the absolute increase in PNa on days 7 and 14. The urea dosing scheme will involve increasing from the starting dose of 15 grams/day to 30 grams/day (in 2 divided doses) based on the change in and absolute value of PNa, and subsequently, from 30 grams/day to 60 grams/day (in 2 divided doses) when indicated. The maximal dose of urea administered will be 60 g/day. | 1 |
| Off Urea, Then On Urea Participants assigned to this group will be off urea during for 42 days (period 1), followed by a 10-day washout period, and then on urea for 42 days (period 2)
Urea: Groups On Urea, Then Off Urea and Off Urea, Then On Urea will receive urea during period 1 and period 2 of the study, respectively. The investigators will use the new American formulation of oral urea (i.e., Ure-Na™), which is packaged as a powder and mixed with 4 ounces. of water for oral consumption. Urea will be started at a dose of 15 grams of urea per mouth once daily. Dose titration will be based on the absolute increase in PNa on days 7 and 14. The urea dosing scheme will involve increasing from the starting dose of 15 grams/day to 30 grams/day (in 2 divided doses) based on the change in and absolute value of PNa, and subsequently, from 30 grams/day to 60 grams/day (in 2 divided doses) when indicated. The maximal dose of urea administered will be 60 g/day. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | On Urea, Then Off Urea | Total | Off Urea, Then On Urea |
|---|---|---|---|
| Accuracy action boundary selection | 32.18 percentage of accuracy | 17.82 percentage of accuracy STANDARD_DEVIATION 20.3 | 3.45 percentage of accuracy |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 0 Participants |
| Amplitude scaling of posture control and stability using dynamic representation of upright stance | 15.922 units on a scale | 20.23 units on a scale STANDARD_DEVIATION 6 | 24.539 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Movement latency of posture control and stability using dynamic representation of upright stance | 4.598 msec | 6.46 msec STANDARD_DEVIATION 3 | 8.331 msec |
| Percentage angular deviation of somatosensory control system using dynamic representation of upright | 0.05 percentage | 1.08 percentage STANDARD_DEVIATION 1 | 2.11 percentage |
| Percentage angular deviation of vestibular control system using dynamic representation of upright st | 141.57 percentage | 98.74 percentage STANDARD_DEVIATION 61 | 55.91 percentage |
| Percentage angular deviation of visual control system using dynamic representation of upright stance | -2.53 percentage | -4.22 percentage STANDARD_DEVIATION 2 | -5.9 percentage |
| Percentage weight symmetry using dynamic representation of upright stance | -9.49 percentage | 2.49 percentage STANDARD_DEVIATION 17 | 14.47 percentage |
| Plasma sodium concentration | 129 mmol/L | 127.5 mmol/L STANDARD_DEVIATION 2.1 | 126 mmol/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment United States | 1 participants | 2 participants | 1 participants |
| Sample entropy of the center of pressure data from the force plate | 6.7 percentage | 3.45 percentage STANDARD_DEVIATION 6 | 0.2 percentage |
| Score of sensorimotor ability battery | 99.78 units on a scale | 61.62 units on a scale STANDARD_DEVIATION 54 | 23.45 units on a scale |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
| SF-12 (Health Survey) Mental Component Summary (MCS) | 59.77660 units on a scale | 58.85 units on a scale STANDARD_DEVIATION 1 | 57.92257 units on a scale |
| SF-12 (Health Survey) Physical Component Summary (PCS) | 54.83583 units on a scale | 54.32 units on a scale STANDARD_DEVIATION 1 | 53.79573 units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 2 / 2 | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Adverse Events Related to Urea
To be assessed by medication side effect questionnaire. A tabulation of counts of participants experiencing specific known side effects of urea as well as their intensity (mild, moderate or severe) will be performed.
Time frame: Baseline to day 42 while taking urea
Population: The measure is only applicable when on urea
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Urea | Adverse Events Related to Urea | Headaches | Severe | 0 Participants |
| Urea | Adverse Events Related to Urea | Diarrhea | Mild | 1 Participants |
| Urea | Adverse Events Related to Urea | Diarrhea | Moderate | 0 Participants |
| Urea | Adverse Events Related to Urea | Diarrhea | Severe | 0 Participants |
| Urea | Adverse Events Related to Urea | Headaches | None | 1 Participants |
| Urea | Adverse Events Related to Urea | Headaches | Mild | 0 Participants |
| Urea | Adverse Events Related to Urea | Nausea | None | 1 Participants |
| Urea | Adverse Events Related to Urea | Nausea | Mild | 0 Participants |
| Urea | Adverse Events Related to Urea | Nausea | Moderate | 1 Participants |
| Urea | Adverse Events Related to Urea | Nausea | Severe | 0 Participants |
| Urea | Adverse Events Related to Urea | Vomiting | None | 2 Participants |
| Urea | Adverse Events Related to Urea | Vomiting | Mild | 0 Participants |
| Urea | Adverse Events Related to Urea | Vomiting | Moderate | 0 Participants |
| Urea | Adverse Events Related to Urea | Vomiting | Severe | 0 Participants |
| Urea | Adverse Events Related to Urea | Diarrhea | None | 1 Participants |
| Urea | Adverse Events Related to Urea | Headaches | Moderate | 1 Participants |
Primary
Change in Amplitude Scaling of Posture Control and Stability Using Dynamic Representation of Upright Stance
Change in amplitude scaling of posture control and stability using dynamic representation of upright stance from baseline to day 42. This will be assessed using the Motor Control Test (MCT). MCT assesses the ability to quickly recover from an unexpected external translation. It is scored in units of angular momentum and normalized to body height and weight. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in ability to recover from an unexpected external translation reflecting better balance.
Time frame: Baseline to day 42
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Amplitude Scaling of Posture Control and Stability Using Dynamic Representation of Upright Stance | 5.414 units on a scale |
| No Urea | Change in Amplitude Scaling of Posture Control and Stability Using Dynamic Representation of Upright Stance | 9.0495 units on a scale |
Primary
Change in Movement Latency of Posture Control and Stability Using Dynamic Representation of Upright Stance
Change in movement latency of posture control and stability using dynamic representation of upright stance from baseline to day 42. This will be assessed using the Motor Control Test (MCT). MCT assesses the ability to quickly recover from an unexpected external translation. Latency scores measure the time lapse between force plate translation on postural response for healthy, elderly populations, with previously reported mean latency values ranging from 126.80-131.40. Higher/Larger scores indicate poorer balance control.
Time frame: Baseline to day 42
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Movement Latency of Posture Control and Stability Using Dynamic Representation of Upright Stance | -3.8245 milliseconds |
| No Urea | Change in Movement Latency of Posture Control and Stability Using Dynamic Representation of Upright Stance | 8.677 milliseconds |
Primary
Change in Overall Score of Sensorimotor Ability Battery
Change in overall score of sensorimotor ability battery from baseline to day 42. This will be measured by the Senaptec Sensory Station™ test battery which examines separate sensorimotor elements including; multiple object tracking, reaction time, perception span, go/no go, depth perception and dynamic visual acuity. Score goes from 0 to1500 with higher scores representing better sensorimotor ability
Time frame: Baseline to day 42
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Overall Score of Sensorimotor Ability Battery | 54.43 score on a scale |
| No Urea | Change in Overall Score of Sensorimotor Ability Battery | 53.6 score on a scale |
Primary
Change in Percentage Accuracy Action Boundary Selection
Change in percentage accuracy action boundary selection from baseline to day 42. This will be measured by the Perception-Action Coupling Task (PACT) which is an affordance-based assessment conducted on an iPad, which uses matched pairs of 'virtual' balls and 'virtual' holes to assess patients' ability to accurately assess their action boundaries. Accuracy of affordance perception is measured. Scores goes from 0% to 100% with higher score representing increased accuracy
Time frame: Baseline to day 42
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Percentage Accuracy Action Boundary Selection | 12.965 percentage accuracy |
| No Urea | Change in Percentage Accuracy Action Boundary Selection | 8.245 percentage accuracy |
Primary
Change in Percentage Angular Deviation of Somatosensory Control System Using Dynamic Representation of Upright Stance
Change in percentage angular deviation of somatosensory control system using dynamic representation of upright stance from baseline to day 42. This will be assessed using the NeuroCom™ Sensory Organization. This test enables both the examination of postural control and stability in response to a direct perturbation of the somatosensory control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the somatosensory system involved in maintaining upright stance in dynamic situations. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in somatosensory balance control.
Time frame: Baseline to day 42
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Percentage Angular Deviation of Somatosensory Control System Using Dynamic Representation of Upright Stance | 1.99 percentage change from baseline |
| No Urea | Change in Percentage Angular Deviation of Somatosensory Control System Using Dynamic Representation of Upright Stance | -0.85 percentage change from baseline |
Primary
Change in Percentage Angular Deviation of Vestibular Control System Using Dynamic Representation of Upright Stance
Change in percentage angular deviation of vestibular control system using dynamic representation of upright stance from baseline to day 42. This was assessed using the NeuroCom™ Sensory Organization. This test enables both the examination of postural control and stability in response to a direct perturbation of the vestibular control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the vestibular system involved in maintaining upright stance in dynamic situations. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in vestibular balance control.
Time frame: Baseline to day 42
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Percentage Angular Deviation of Vestibular Control System Using Dynamic Representation of Upright Stance | 112.23 percentage |
| No Urea | Change in Percentage Angular Deviation of Vestibular Control System Using Dynamic Representation of Upright Stance | 88.0455 percentage |
Primary
Change in Percentage Angular Deviation of Visual Control System Using Dynamic Representation of Upright Stance
Change in percentage angular deviation of visual control system using dynamic representation of upright stance from baseline to day 42. This will be assessed using the NeuroCom™ Sensory Organization. This test enables both the examination of postural control and stability in response to a direct perturbation of the visual control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the visual system involved in maintaining upright stance in dynamic situations. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in visual balance control.
Time frame: Baseline to 42 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Percentage Angular Deviation of Visual Control System Using Dynamic Representation of Upright Stance | -1.1735 percentage change from baseline |
| No Urea | Change in Percentage Angular Deviation of Visual Control System Using Dynamic Representation of Upright Stance | -7.3825 percentage change from baseline |
Primary
Change in Percentage Weight Symmetry Using Dynamic Representation of Upright Stance
Change in percentage weight symmetry using dynamic representation of upright stance from baseline to day 42. This will be assessed using the Motor Control Test (MCT). MCT assesses the ability to quickly recover from an unexpected external translation. Weight symmetry indicates weight distribution under the left and right legs prior to perturbation onset. A score of 100 indicates perfect between-limb symmetry. Larger deviations away (higher or Lower) from 100 indicate asymmetry. Scores goes from -100 to +100 closer to 100 is optimal.
Time frame: Baseline to day 42
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Percentage Weight Symmetry Using Dynamic Representation of Upright Stance | -1.6255 percentage change from baseline |
| No Urea | Change in Percentage Weight Symmetry Using Dynamic Representation of Upright Stance | 2.5 percentage change from baseline |
Primary
Change in Plasma Sodium Concentration
Change in plasma sodium concentration from baseline to day 42. Based on plasma sodium assessments on days 0 and 42.
Time frame: Baseline to day 42
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in Plasma Sodium Concentration | 2.5 mmol/L |
| No Urea | Change in Plasma Sodium Concentration | 0.5 mmol/L |
Primary
Change in the Sample Entropy of the Center of Pressure Data From the Force Plate
Measure the 'structure' of the noise in the oscillations of the center of mass of the individual. The measurement represent the percentage of displacement from the center of pressure. No reference ranges are available as these vary according to the population studied
Time frame: Baseline to day 42
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in the Sample Entropy of the Center of Pressure Data From the Force Plate | 4.3 percentage change from baseline |
| No Urea | Change in the Sample Entropy of the Center of Pressure Data From the Force Plate | 1.3 percentage change from baseline |
Primary
Monthly Enrollment Rate
Number of participants enrolled in the study every month. To be assessed by analysis of enrollment data
Time frame: 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Urea | Monthly Enrollment Rate | 0.07 participants per month | Standard Deviation 0 |
| No Urea | Monthly Enrollment Rate | 0.07 participants per month | Standard Deviation 0 |
Primary
Number and Percentage of Participants Enrolled Who Completed the Study
Number and percentage of participants enrolled who completed the study. To be assessed by analysis of enrollment and completion data.
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Urea | Number and Percentage of Participants Enrolled Who Completed the Study | 2 Participants |
| No Urea | Number and Percentage of Participants Enrolled Who Completed the Study | 2 Participants |
Primary
Number and Percentage of Participants Who Met Inclusion/Exclusion Criteria and Were Enrolled in the Study
Number and percentage of participants who met inclusion/exclusion criteria and were enrolled in the study. To be assessed by analysis of enrollment data.
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Urea | Number and Percentage of Participants Who Met Inclusion/Exclusion Criteria and Were Enrolled in the Study | 2 Participants |
| No Urea | Number and Percentage of Participants Who Met Inclusion/Exclusion Criteria and Were Enrolled in the Study | 2 Participants |
Primary
Number and Proportion of Participants Enrolled in the Study With Adverse Events Related to the Use of Urea
Number and proportion of participants enrolled in the study with adverse events related to the use of urea from baseline to day 42. To be assessed by medication side effect questionnaire.
Time frame: Baseline to day 42 while taking urea
Population: This measure is only relevant when on urea
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Urea | Number and Proportion of Participants Enrolled in the Study With Adverse Events Related to the Use of Urea | 1 Participants |
| No Urea | Number and Proportion of Participants Enrolled in the Study With Adverse Events Related to the Use of Urea | 0 Participants |
Primary
Number of Prescribed Urea Doses Taken by Participants
Number of prescribed urea doses taken by participants. To be assessed by records in study diary and number of returned medication doses.
Time frame: Baseline to day 42 while taking urea
Population: The measure is only applicable when on urea
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Number of Prescribed Urea Doses Taken by Participants | 61.5 15-g urea packets |
Primary
Reasons for Non-Adherence to Urea Therapy
Reasons for non-adherence to urea therapy. To be assessed by medication acceptability and medication side effect questionnaires
Time frame: Baseline to day 42 while taking urea
Population: The measure is only applicable when on urea
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Urea | Reasons for Non-Adherence to Urea Therapy | Medication tastes poorly | 2 Participants |
| Urea | Reasons for Non-Adherence to Urea Therapy | Inconvenient medication dose frequency | 2 Participants |
| Urea | Reasons for Non-Adherence to Urea Therapy | Inconvenient medication amount | 1 Participants |
| Urea | Reasons for Non-Adherence to Urea Therapy | Medication is unsuitable to take outside home | 2 Participants |
| Urea | Reasons for Non-Adherence to Urea Therapy | Medications makes me feel sick | 1 Participants |
Secondary
Average Ratings for Medication Acceptability
Average ratings using a 5-point Likert scale medication acceptability questionnaire. in which responders specify their level of agreement to a statement in five points: (1) Strongly disagree; (2) Disagree; (3) Neutral; (4) Agree; (5) Strongly agree; or (1) Very Unhappy; (2) Unhappy; (3) Neutral; (4) Happy; (5) Very Happy. A higher overall score represents more acceptability
Time frame: Baseline to day 42 while taking urea
Population: The measure is only applicable when on urea
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Average Ratings for Medication Acceptability | 2.725 units on a 5-point Likert scale |
Secondary
Change in SF-12 (Health Survey) Mental Component Summary (MCS)
Change in SF-12 (Health Survey) Mental Component Summary (MCS) from baseline to day 42. Based on SF-12 MCS assessments on days 0 and 42. This is computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: Baseline to day 42
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in SF-12 (Health Survey) Mental Component Summary (MCS) | 1.435 score on SF-12 scale |
| No Urea | Change in SF-12 (Health Survey) Mental Component Summary (MCS) | 0.745 score on SF-12 scale |
Secondary
Change in SF-12 (Health Survey) Physical Component Summary (PCS)
Change in SF-12 (Health Survey) Physical Component Summary (PCS) from baseline to day 42. Based on SF-12 PCS assessments on days 0 and 42. This is computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: Baseline to day 42
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Urea | Change in SF-12 (Health Survey) Physical Component Summary (PCS) | -2.105 score on a SF-12 scale |
| No Urea | Change in SF-12 (Health Survey) Physical Component Summary (PCS) | -3.25 score on a SF-12 scale |
Secondary
Number and Percentage of Patients Screened Who Met Inclusion/Exclusion Criteria for the Study
Number and percentage of patients screened who met inclusion/exclusion criteria for the study. To be assessed by analysis of screening and enrollment data.
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Urea | Number and Percentage of Patients Screened Who Met Inclusion/Exclusion Criteria for the Study | 2 Participants |
Secondary
Number and Proportion of Participants Who Thought the Medication Was Acceptable
Number and proportion of participants who thought the medication was acceptable. Based on ratings for acceptability in the medication acceptability questionnaire.
Time frame: Baseline to day 42 while taking urea
Population: All participants who received at least one dose of each intervention and completed all study visits were included
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Urea | Number and Proportion of Participants Who Thought the Medication Was Acceptable | 1 Participants |
| No Urea | Number and Proportion of Participants Who Thought the Medication Was Acceptable | 0 Participants |
Secondary
Number and Proportion of Participants Who Took More Than 80 Percent of Prescribed Urea Doses
Number and proportion of participants who took more than 80 percent of prescribed urea doses. To be assessed by analysis of study diary and number of returned medication doses.
Time frame: Baseline to day 42 while taking urea
Population: All participants who received at least one dose of each intervention and completed all study visits were included. The measure is only applicable when on urea.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Urea | Number and Proportion of Participants Who Took More Than 80 Percent of Prescribed Urea Doses | 1 Participants |
Secondary
Number of Patients Screened
Number of patients screened. To be assessed by analysis of screening data.
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Urea | Number of Patients Screened | 1213 Participants |