Protocol summary
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Study aim
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To determine the effects of N-Acetyl-l-Leucine on the improvement of symptoms in patients with ataxia-telangiectasia
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Design
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The current study is a randomized, double-blind, crossover clinical trial with parallel groups. A total of 16 subjects are enrolled between Dec.6. 2021 and Aug.6.2022. The table of random numbers was used for randomization.
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Settings and conduct
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Patients with ataxia-telangiectasia who referring to Neurology Clinic of the Ghaem Hospital are enrolled in the study. All volunteers, care providers and statistician are blinded after assignment to intervention. So that, the supplements containers were coded as A and B by a non-researcher person and remained confidential until data analysis. The placebos caplets are similar to the supplements regarding the weight and color.
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Participants/Inclusion and exclusion criteria
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Inclusion criteria: Patients with a definitive diagnosis of ataxia telangiectasia having clinical signs and not having addiction, the patients should be on a stable dose/duration and type of speech therapy or physiotherapy. Exclusion criteria: Patients having chronic diarrhea, visual loss, malignancies, insulin-dependent diabetes mellitus, known history of hypersensitivity to the N-Acetyl-Leucine, Having severe vision or hearing impairment, Having a definite diagnosis of arthritis or other musculoskeletal disorders.
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Intervention groups
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In treatment group (n=8), N-acetyl-L-leucine caplet is taken orally in subjects with ataxia-telangiectasia for 6 weeks and then after a 4-weeks wash-out period, they were crossed over to the alternate regimen.
In the control group (n=8), placebo caplet of the same shape, weight and colour is used in patients with ataxia-telangiectasia for 6 weeks and then after a 4-weeks wash-out period, they were crossed over to the alternate regimen.
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Main outcome variables
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Movement signs
General information
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Reason for update
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-Due to prepare the caplets and not taking sachets, the powder has changed to caplet.
-Moreover, due to the unwanted delay in the custom release of the drug, the patients recruitment was extended.
-Also, according to a valid evidence in Europe, the supplement dose was adjusted from 1 to 6 grams more precisely to 1 to 4 grams, depending on the patient's weight.
-Food recall will also be recorded in patients at each stage of the study.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20210413050958N1
Registration date:
2021-10-27, 1400/08/05
Registration timing:
prospective
Last update:
2021-11-25, 1400/09/04
Update count:
1
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Registration date
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2021-10-27, 1400/08/05
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2021-12-06, 1400/09/15
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Expected recruitment end date
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2022-08-06, 1401/05/15
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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The effects of N-Acetyl-l-Leucine on the improvement of symptoms in patients with ataxia-telangiectasia: A double-blind crossover trial
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Public title
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Effect of N-Acetyl-l-Leucine in treatment of ataxia-telangiectasia
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Signed informed consent form by the subjects or their parents after explaining the study objectives by the research team
Patients with a definitive diagnosis of AT
Having clinical signs
Not addiction to Drugs and alcohol
If the patient is receiving concomitant speech therapy or physiotherapy, he/she has been on a stable dose/duration and type of therapy for at least 4 weeks before visit 1 and throughout the duration of the study
If the patient is taking any medication, he/she should maintain a constant dose/not change his/her treatment during the study period.
Exclusion criteria:
Have not taken any forbidden drugs (including any variant of N-acetyl-DL-leucine, aminopyridines, Riluzole, gabapentin, Varenicline, Chlorzoxazone, sulfasalazine, Rosuvastatin at least 4 weeks before visit 1 and throughout the duration of the study
Asymptomatic patients
Patient who have clinical signs of A-T, but do not have a confirmed genetic test for A-T
Patients who have any of the following: Chronic diarrhea, Unexplained visual loss, Malignancies, Insulin-dependent diabetes mellitus, Known history of hypersensitivity to the N-Acetyl-Leucine (DL-, L-, D-) or derivatives
Having severe vision or hearing impairment that interferes with their ability to complete study assessments
Having a definite diagnosis of arthritis or other musculoskeletal disorders that affects patient's mobility and interferes with their ability to complete study assessments
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Age
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No age limit
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Gender
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Both
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Phase
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2
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Groups that have been masked
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- Participant
- Care provider
- Investigator
- Data analyser
- Data and Safety Monitoring Board
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Sample size
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Target sample size:
16
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Regarding the presence of the gender as a confounder, we run the block randomization method within each category (male and female) separately. For this reason, inside each category, blocks with size 4 and 2 of the combination of letters A and B
(ABBA, ABAB, AABB, BAAB, BBAA, BABA), (AB and BA) are selected to the required number using a table of random numbers and individuals are assigned to groups according to the created sequence.
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Blinding (investigator's opinion)
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Triple blinded
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Blinding description
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The random allocation sequence is made using the table of random numbers. Sequentially numbered sealed envelopes are used to implement the random allocation sequence which opened by a person not involved in the project. The participants, care providers and statistician are blinded after assignment to intervention. So that, the caplet bottles are coded by a non-researcher person and remain confidential until data analysis. Moreover, In addition, placebo caplet is similar to supplement ones in shape, weight and color.
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Placebo
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Used
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Assignment
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Crossover
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2021-08-24, 1400/06/02
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Ethics committee reference number
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IR.MUMS.MEDICAL.REC.1400.389
Health conditions studied
1
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Description of health condition studied
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Ataxia-Telangiectasia
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ICD-10 code
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G11.3
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ICD-10 code description
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Cerebellar ataxia with defective DNA repair
Primary outcomes
1
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Description
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Movement signs
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Using the Scale for Assessment and Rating of Ataxia (SARA) score and Spinocerebellar Ataxia Functional Index (SCAFI)
Secondary outcomes
1
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Description
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The quality of life
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Using PedsQL questionnaire
2
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Description
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Cell blood count
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Sysmex Cell Counter
3
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Description
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Lactate dehydrogenase
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
4
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Description
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Aspartate aminotransferase
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
5
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Description
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Alanine aminotransferase
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
6
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Description
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Urea
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
7
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Description
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Creatinine
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
8
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Description
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Alkaline phosphatase
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
9
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Description
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Na
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
10
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Description
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k
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
11
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Description
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Total bilirubin
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
12
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Description
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Direct bilirubin
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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Auto analyzer instrument
13
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Description
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Food recall
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Timepoint
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Before the intervention and 6 weeks after taking supplement or placebo in every study stage
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Method of measurement
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24-hour food recall tool
Intervention groups
1
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Description
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Intervention group: Subjects in the intervention group receive N-Acetyl-L-Leucine caplets (daily intake of 1-4 gr depending on the subjects’ weight) for 6 weeks (n=8) and then after a 4-weeks wash-out period, they were crossed over to the alternate regimen. The participants take the supplement every day, which was contained in an unlabeled bottle. Supplements are from Hubei ipure Biotech co., ltd (Shenzhen, China).
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Category
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Treatment - Drugs
2
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Description
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Control group: The control group received the placebo (daily consumption between 1 to 4 grams depending on the subject's weight) for 6 weeks (n=8) and then after a 4-weeks wash-out period, they were crossed over to the alternate regimen. Participants take a placebo every day orally in an unlabeled bottle. The placebo is prepared by from faculty of pharmacy (Mashhad, Iran) company.
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Category
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Placebo
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Mashhad University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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No - There is not a plan to make this available
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Justification/reason for indecision/not sharing IPD
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Raw data will be shared upon a reasonable request from the corresponding author.
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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No - There is not a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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No - There is not a plan to make this available
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Data Dictionary
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No - There is not a plan to make this available
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Title and more details about the data/document
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Following a reasonable request, deidentified data will be shared.
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When the data will become available and for how long
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After publication of paper(s) upon a reasonable request
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To whom data/document is available
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Study PI and executive team
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Under which criteria data/document could be used
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For reasonable research or clinical purpose
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From where data/document is obtainable
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Maryam Saberi-Karimian
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What processes are involved for a request to access data/document
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Direct e-mail
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Comments
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Moreover, if necessary, other unforeseen genetic, immunologic, biochemical and nutritional assays will be performed in the future only for research purposes on frozen samples.