Back to resultsThe Effect of Vitamin C and E Therapy on Restless Leg Syndrome in Patients With End Stage Renal Disease on Haemodialysis
Primary Purpose
Restless Legs Syndrome, End Stage Renal Disease
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ascorbic acid
Tocopherol
Placebo capsule
Placebo capsule
Sponsored by
About this trial
This is an interventional treatment trial for Restless Legs Syndrome
Eligibility Criteria
Inclusion Criteria:
- End stage renal disease patients on hemodialysis who met the five diagnostic criteria of RLS.
Exclusion Criteria:
- Secondary causes of RLS Medications (list included in section C below) iron deficiency or peripheral neuropathy
Presence of RLS-mimicking disorders:
- Arthritis
- Deep venous thrombosis
- Varicose veins or venous insufficiency
- Habitual foot tapping
Patients receiving medications that could trigger RLS:
- Anticonvulsants, e.g., new use of anticonvulsant drugs within6 months of screening. A stable regimen of anticonvulsants was allowed.
- Antipsychotics (haloperidol or phenothiazine derivatives)
- Antidepressants (selective serotonin reuptake inhibitors or tricyclic antidepressants)
- Antimanic (lithium)
Patients on medications or with conditions that may interfere with vitamin C & E absorption:
- Celiac disease
- Crohn's disease
- Chronic pancreatitis
- Cystic fibrosis
- Weight-reduction drugs
- Chemotherapy and radiotherapy
Patients with contraindications for vitamin C & E supplements:
- Blood disorders, e.g., thalassemia, G6PD, sickle cell disease and hemochromatosis
- Other conditions like diabetic patients, oxalate nephropathy, nephrolithiasis and vitamin E or C allergy
- Unstable vital signs
- Retinal eye disease
- Cancers
- Liver disease
- Vitamin K deficiency
For women only:
- Pregnancy (positive pregnancy test at screening)
- Currently breastfeeding
- Use of oral contraceptives or start of menopausal hormone therapy within 3 months of baseline
History of vitamin E or C intolerance
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1
Group 2
Group 3
Group 4
Arm Description
Vitamin C (200 mg) capsule, and vitamin E (400 IU) capsule every day for 12 weeks.
Vitamin C (200 mg) capsule, and placebo every day for 12 weeks.
Vitamin E (400 IU) capsule, and placebo every day for 12 weeks.
Placebo capsule (2 pills) every day for 12 weeks.
Outcomes
Primary Outcome Measures
International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria
The IRLSSG is a validated and reliable questionnaire. Well-trained physicians will aid patients in completing this questionnaire and perform clinical examination. It consists of five yes/no questions, subjects will be considered to have RLS if their answers are yes to all five questions
Stop Bang
The STOP-Bang questionnaire includes the four questions used in the STOP questionnaire plus four additional demographic queries, for a total of eight dichotomous (yes/no) questions related to the clinical features of sleep apnea (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference and male gender). For each question, answering "yes" scores 1, a "no" response scores 0, and the total score ranges from 0 to 8.
Low Risk: Yes to 0 - 2 questions
Intermediate Risk: Yes to 3 - 4 questions
High Risk: Yes to 5 - 8 questions
or Yes to 2 or more of 4 STOP questions + male gender
or Yes to 2 or more of 4 STOP questions + BMI > 35kg/m2
or Yes to 2 or more of 4 STOP questions + neck circumference 16 inches / 40cm
Hemoglobin
Participants with normal levels between 12 - 15 g/dl Participants with levels below 12 or above 15 will be considered abnormal
Changes in The International Restless Leg Syndrome Study Group (IRLSSG) rating scale for restless legs syndrome
That consists of 10 questions scored from 0-4 with a total score ranging from 0-40 in which RLS severity is directly proportional to the total score. Meaning the higher the score, the worse and severe the symptoms.
Epworth sleepiness scale (ESS)
It is a self-administered questionnaire that measures the severity of excessive daytime sleepiness (EDS) containing 8 questions, each question is given a score from 0 to 3 with a total score of 0-24. A score above 10 is considered abnormal i.e. in keeping with EDS
Medical Outcomes Study Sleep Scale (MOS)
A 12-item scale that investigates six factors including; sleep initiation, respiratory problems, maintenance, perceived adequacy and somnolence. With higher score indicating higher sleep disturbance.
Suggested Immobilization Test (SIT)
prior to the sleep recording. at 45-degree angle with their legs outstretched. avoid moving voluntarily for the entire duration of the test. Surface EMG from the left and right anterior tibialis muscles is used to quantify leg movements. The latter are scored according to the criteria (movements lasting between 0.5 and 10 seconds, separated by intervals of 4 to 90 seconds and arising in series of at least 4 consecutive movements). The SIT periodic leg movements index represents the number of periodic leg movements per hour of immobility. Patients report severity of leg discomfort on a visual analogue scale (VAS) ranging from 0 (no discomfort) to 100 (extreme discomfort) every 10 minutes during the SIT. The mean leg discomfort score is assessed using the average of the 7 values, as well as the discomfort severity at the end of the test (time 60 minutes), the maximum leg discomfort during the test, and the variation between the lowest and the highest values recorded during the test
Restless Leg Syndrome (RLS) Symptoms Diary
The (RLS) Symptom Diary is a convenient tool to record information on your daily (RLS) symptoms, their duration, sleep patterns and possible triggers such as nicotine, alcohol or caffeine. to identify what influences, triggers or worsen the (RLS) symptoms
Polysomnography
Polysomnography (SOMNO Medics Plus; SOMNOmedics, Randersacker, Germany) consists of continuous recordings from surface leads for electroencephalography (EEG), electrooculography, electromyography (submental and bilateral anterior tibialis muscles), electrocardiography, nasal pressure, nasal and oral airflow (thermocouple), chest and abdominal impedance belts for respiratory muscle efforts, pulse oximetry for oxygen saturation and pulse rate, a tracheal microphone for snoring, and body position sensors for sleep position. PSG records are scored manually according to the American Academy of Sleep Medicine (AASM) 2020 scoring
Hemoglobin A1C
Participants will be considered normal if the level is within 4.2 - 6.3 % Participants with a level higher than 6.3% will be considered abnormal
Vitamin D
Participants will be considered normal if the level is within 75 - 250 nmol/L Participants will be considered abnormal if the level is less than 75 or higher than 250 nmol/L
Serum Iron
Participants will be considered normal if the level is within 6 - 26 umol/L
Total Iron Binding Capacity
Participants will be considered normal if the level is within 25 - 92 umol/L
Ferritin
Participants will be considered normal if the level is within 13-150 ng/ml
Magnesium
Participants will be considered normal if the level is within 1.7 - 2.2 mg/dL
Secondary Outcome Measures
Full Information
NCT ID
NCT05350124
First Posted
March 17, 2022
Last Updated
August 22, 2022
Sponsor
King Abdulaziz University
1. Study Identification
Unique Protocol Identification Number
NCT05350124
Brief Title
The Effect of Vitamin C and E Therapy on Restless Leg Syndrome in Patients With End Stage Renal Disease on Haemodialysis
Official Title
The Effect of Vitamin C and E Therapy on Restless Leg Syndrome in Patients With End Stage Renal Disease on Haemodialysis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2022 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
King Abdulaziz University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study aims to measure the effectiveness of vitamins C and E on relieving RLS symptoms in end stage renal disease patients on HD
Detailed Description
double-blind placebo-controlled trial of 12 weeks duration on end stage renal disease (ESRD) patients on HD with RLS.
All ESRD patients on HD will be screened clinically for RLS using the five diagnostic criteria of IRLSSG by trained physicians. then the Quastioniare will be filled and inclusion and exclusion criteria be checked sleep study must be done.
Each patient will then undergo a full sleep study using level 2 polysomnography at home. Periodic leg movements with sleep (PLMs) index and leg movements index (LM) before sleep onset will be recorded as well as other variables
Then Subjects will then be randomly assigned by blocked randomization into four groups, each group will include 40 patients. A. Group 1: Will receive vitamin C (200 mg) tablet and vitamin E (a-tocopherol) (400 mg) capsule every day for 12 weeks. B. Group 2: Will receive vitamin E (400 mg) capsule and placebo every day for 12 weeks.
C. Group 3: Will receive vitamin C (200 mg) tablet and placebo every day for 12 weeks. D. Group 4: Will receive two placebo every day for 12 weeks. Of note, the personal responsible for randomization will not be involved in the trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Restless Legs Syndrome, End Stage Renal Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
randomization into four groups, each group will include 40 patients. A. Group 1: Will receive vitamin C (200 mg) tablet and vitamin E (a-tocopherol) (400 mg) capsule every day for 12 weeks. B. Group 2: Will receive vitamin E (400 mg) capsule and placebo every day for 12 weeks.
C. Group 3: Will receive vitamin C (200 mg) tablet and placebo every day for 12 weeks. D. Group 4: Will receive two placebo every day for 12 weeks. Of note, the personal responsible for randomization will not be involved in the trial.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Vitamin C (200 mg) capsule, and vitamin E (400 IU) capsule every day for 12 weeks.
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Vitamin C (200 mg) capsule, and placebo every day for 12 weeks.
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Vitamin E (400 IU) capsule, and placebo every day for 12 weeks.
Arm Title
Group 4
Arm Type
Experimental
Arm Description
Placebo capsule (2 pills) every day for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Ascorbic acid
Other Intervention Name(s)
Vitamin C
Intervention Description
vitamin C (200 mg) capsule
Intervention Type
Drug
Intervention Name(s)
Tocopherol
Other Intervention Name(s)
Vitamin E
Intervention Description
vitamin E (400 IU) capsule
Intervention Type
Drug
Intervention Name(s)
Placebo capsule
Other Intervention Name(s)
Inactive substance
Intervention Description
Placebo one pill only
Intervention Type
Drug
Intervention Name(s)
Placebo capsule
Other Intervention Name(s)
Inactive substance
Intervention Description
Placebo two pills only
Primary Outcome Measure Information:
Title
International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria
Description
The IRLSSG is a validated and reliable questionnaire. Well-trained physicians will aid patients in completing this questionnaire and perform clinical examination. It consists of five yes/no questions, subjects will be considered to have RLS if their answers are yes to all five questions
Time Frame
in screening
Title
Stop Bang
Description
The STOP-Bang questionnaire includes the four questions used in the STOP questionnaire plus four additional demographic queries, for a total of eight dichotomous (yes/no) questions related to the clinical features of sleep apnea (snoring, tiredness, observed apnea, high blood pressure, BMI, age, neck circumference and male gender). For each question, answering "yes" scores 1, a "no" response scores 0, and the total score ranges from 0 to 8.
Low Risk: Yes to 0 - 2 questions
Intermediate Risk: Yes to 3 - 4 questions
High Risk: Yes to 5 - 8 questions
or Yes to 2 or more of 4 STOP questions + male gender
or Yes to 2 or more of 4 STOP questions + BMI > 35kg/m2
or Yes to 2 or more of 4 STOP questions + neck circumference 16 inches / 40cm
Time Frame
in screening
Title
Hemoglobin
Description
Participants with normal levels between 12 - 15 g/dl Participants with levels below 12 or above 15 will be considered abnormal
Time Frame
in screening
Title
Changes in The International Restless Leg Syndrome Study Group (IRLSSG) rating scale for restless legs syndrome
Description
That consists of 10 questions scored from 0-4 with a total score ranging from 0-40 in which RLS severity is directly proportional to the total score. Meaning the higher the score, the worse and severe the symptoms.
Time Frame
base line then once weekly for 12 weeks
Title
Epworth sleepiness scale (ESS)
Description
It is a self-administered questionnaire that measures the severity of excessive daytime sleepiness (EDS) containing 8 questions, each question is given a score from 0 to 3 with a total score of 0-24. A score above 10 is considered abnormal i.e. in keeping with EDS
Time Frame
base line then once every 4 weeks for 12 weeks
Title
Medical Outcomes Study Sleep Scale (MOS)
Description
A 12-item scale that investigates six factors including; sleep initiation, respiratory problems, maintenance, perceived adequacy and somnolence. With higher score indicating higher sleep disturbance.
Time Frame
base line then once every 4 weeks for 12 weeks
Title
Suggested Immobilization Test (SIT)
Description
prior to the sleep recording. at 45-degree angle with their legs outstretched. avoid moving voluntarily for the entire duration of the test. Surface EMG from the left and right anterior tibialis muscles is used to quantify leg movements. The latter are scored according to the criteria (movements lasting between 0.5 and 10 seconds, separated by intervals of 4 to 90 seconds and arising in series of at least 4 consecutive movements). The SIT periodic leg movements index represents the number of periodic leg movements per hour of immobility. Patients report severity of leg discomfort on a visual analogue scale (VAS) ranging from 0 (no discomfort) to 100 (extreme discomfort) every 10 minutes during the SIT. The mean leg discomfort score is assessed using the average of the 7 values, as well as the discomfort severity at the end of the test (time 60 minutes), the maximum leg discomfort during the test, and the variation between the lowest and the highest values recorded during the test
Time Frame
base line then once every 4 weeks for 12 weeks
Title
Restless Leg Syndrome (RLS) Symptoms Diary
Description
The (RLS) Symptom Diary is a convenient tool to record information on your daily (RLS) symptoms, their duration, sleep patterns and possible triggers such as nicotine, alcohol or caffeine. to identify what influences, triggers or worsen the (RLS) symptoms
Time Frame
base line then daily for the last 2 weeks
Title
Polysomnography
Description
Polysomnography (SOMNO Medics Plus; SOMNOmedics, Randersacker, Germany) consists of continuous recordings from surface leads for electroencephalography (EEG), electrooculography, electromyography (submental and bilateral anterior tibialis muscles), electrocardiography, nasal pressure, nasal and oral airflow (thermocouple), chest and abdominal impedance belts for respiratory muscle efforts, pulse oximetry for oxygen saturation and pulse rate, a tracheal microphone for snoring, and body position sensors for sleep position. PSG records are scored manually according to the American Academy of Sleep Medicine (AASM) 2020 scoring
Time Frame
base line then once every 4 weeks for 12 weeks
Title
Hemoglobin A1C
Description
Participants will be considered normal if the level is within 4.2 - 6.3 % Participants with a level higher than 6.3% will be considered abnormal
Time Frame
In screening
Title
Vitamin D
Description
Participants will be considered normal if the level is within 75 - 250 nmol/L Participants will be considered abnormal if the level is less than 75 or higher than 250 nmol/L
Time Frame
In screening
Title
Serum Iron
Description
Participants will be considered normal if the level is within 6 - 26 umol/L
Time Frame
In screening
Title
Total Iron Binding Capacity
Description
Participants will be considered normal if the level is within 25 - 92 umol/L
Time Frame
In screening
Title
Ferritin
Description
Participants will be considered normal if the level is within 13-150 ng/ml
Time Frame
In screening
Title
Magnesium
Description
Participants will be considered normal if the level is within 1.7 - 2.2 mg/dL
Time Frame
In screening
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
End stage renal disease patients on hemodialysis who met the five diagnostic criteria of RLS.
Exclusion Criteria:
Secondary causes of RLS Medications (list included in section C below) iron deficiency or peripheral neuropathy
Presence of RLS-mimicking disorders:
Arthritis
Deep venous thrombosis
Varicose veins or venous insufficiency
Habitual foot tapping
Patients receiving medications that could trigger RLS:
Anticonvulsants, e.g., new use of anticonvulsant drugs within6 months of screening. A stable regimen of anticonvulsants was allowed.
Antipsychotics (haloperidol or phenothiazine derivatives)
Antidepressants (selective serotonin reuptake inhibitors or tricyclic antidepressants)
Antimanic (lithium)
Patients on medications or with conditions that may interfere with vitamin C & E absorption:
Celiac disease
Crohn's disease
Chronic pancreatitis
Cystic fibrosis
Weight-reduction drugs
Chemotherapy and radiotherapy
Patients with contraindications for vitamin C & E supplements:
Blood disorders, e.g., thalassemia, G6PD, sickle cell disease and hemochromatosis
Other conditions like diabetic patients, oxalate nephropathy, nephrolithiasis and vitamin E or C allergy
Unstable vital signs
Retinal eye disease
Cancers
Liver disease
Vitamin K deficiency
For women only:
Pregnancy (positive pregnancy test at screening)
Currently breastfeeding
Use of oral contraceptives or start of menopausal hormone therapy within 3 months of baseline
History of vitamin E or C intolerance
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Siraj Wali
Phone
0966505606100
Email
sowali@kau.edu.sa
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Effect of Vitamin C and E Therapy on Restless Leg Syndrome in Patients With End Stage Renal Disease on Haemodialysis
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