Stated aim

“The current study assessed the efficacy of NALL in patients with AT.” (opens the source at this quote in a new tab)

“To determine the effects of N-Acetyl-l-Leucine on the improvement of symptoms in patients with ataxia-telangiectasia” (opens the source at this quote in a new tab)

Background to the trial

“Although N-acetyl-dl-leucine (ADLL) has shown some efficacy in patients with AT, its more pharmacologically active enantiomer, N-acetyl-l-leucine (NALL), has just recently been investigated in ataxic individuals.” (opens the source at this quote in a new tab)

Recruitment site and enrollment period

“Patients with ataxia-telangiectasia who referring to Neurology Clinic of the Ghaem Hospital are enrolled in the study.” (opens the source at this quote in a new tab)
“A total of 16 subjects are enrolled between Dec.6. 2021 and Aug.6.2022.” (opens the source at this quote in a new tab)

Registry record

Field	Quoted record
Registration number	“IRCT20210413050958N1”
Registration date	“2021-10-27, 1400/08/05”
Registration timing	“prospective”
Recruitment status	“Recruitment complete”
Expected recruitment start date	“2021-12-06, 1400/09/15”
Expected recruitment end date	“2022-08-06, 1401/05/15”
Recruitment center	“Ghaem Hospital”
City	“Mashhad”
Sponsor and funding source	“Mashhad University of Medical Sciences”

Randomized, double-blind, placebo-controlled, two-period crossover trial

“This 2 × 2 crossover, double-blind, randomized clinical trial was conducted on 20 patients with AT.” (opens the source at this quote in a new tab)
“Subjects then had a 4-week washout before crossing over to the other treatment for an additional six weeks.” (opens the source at this quote in a new tab)

Design field	Quoted record
Phase	“2”
Assignment	“Crossover”
Placebo	“Used”
Blinding (investigator's opinion)	“Triple blinded”
Target sample size	“16”

Randomization stratified by sex

“Regarding the presence of the gender as a confounder, we run the block randomization method within each category (male and female) separately.” (opens the source at this quote in a new tab)
“Sequentially numbered sealed envelopes are used to implement the random allocation sequence which opened by a person not involved in the project.” (opens the source at this quote in a new tab)

Blinding and placebo matching

“The participants, care providers and statistician are blinded after assignment to intervention.” (opens the source at this quote in a new tab)
“The placebos caplets are similar to the supplements regarding the weight and color.” (opens the source at this quote in a new tab)

Registry inclusion criteria

Criterion	Quoted record
Diagnosis	“Patients with a definitive diagnosis of AT”
Symptoms	“Having clinical signs”
Age	“No age limit”
Supportive therapy	“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”
Concomitant medication	“If the patient is taking any medication, he/she should maintain a constant dose/not change his/her treatment during the study period.”

Registry exclusion criteria

Criterion	Quoted record
Symptom status	“Asymptomatic patients”
Genetic confirmation	“Patient who have clinical signs of A-T, but do not have a confirmed genetic test for A-T”
Comorbidity	“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”
Sensory impairment	“Having severe vision or hearing impairment that interferes with their ability to complete study assessments”
Musculoskeletal disorder	“Having a definite diagnosis of arthritis or other musculoskeletal disorders that affects patient's mobility and interferes with their ability to complete study assessments”

Genetic diagnosis in the randomized participants

“After excluding four patients, 16 subjects (eight females, eight males; mean age 9.8 ± 3.5 years) with a definitive genetic diagnosis of AT were randomly assigned to one of two study groups, with one group receiving 1-4 g/day NALL or a placebo for six weeks.” (opens the source at this quote in a new tab)

N-acetyl-L-leucine and placebo regimens

“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.” (opens the source at this quote in a new tab)
“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.” (opens the source at this quote in a new tab)

Source of the study product and placebo

“Supplements are from Hubei ipure Biotech co., ltd (Shenzhen, China).” (opens the source at this quote in a new tab)
“The placebo is prepared by from faculty of pharmacy (Mashhad, Iran) company.” (opens the source at this quote in a new tab)

Changes to formulation and dose recorded in the registry update

“Due to prepare the caplets and not taking sachets, the powder has changed to caplet.” (opens the source at this quote in a new tab)
“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.” (opens the source at this quote in a new tab)

Prohibited medications

“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” (opens the source at this quote in a new tab)

Primary outcome and its measurement

Field	Quoted record
Description	“Movement signs”
Timepoint	“Before the intervention and 6 weeks after taking supplement or placebo in every study stage”
Method of measurement	“Using the Scale for Assessment and Rating of Ataxia (SARA) score and Spinocerebellar Ataxia Functional Index (SCAFI)”

“The Spinocerebellar Ataxia Functional Index (SCAFI) and the Scale for Assessment and Rating of Ataxia (SARA) score assessed patients' motor function.” (opens the source at this quote in a new tab)

Secondary outcomes

Outcome	Method of measurement
“The quality of life”	“Using PedsQL questionnaire”
“Cell blood count”	“Sysmex Cell Counter”
“Aspartate aminotransferase”	“Auto analyzer instrument”
“Food recall”	“24-hour food recall tool”

Systematic review comment on ataxia scales in ataxia-telangiectasia

“Most quantitative clinical ataxia scales employed in the included studies were validated in populations with slower disease progression than AT” (opens the source at this quote in a new tab)

Target sample size and participants randomized

Population	Quoted record
Target sample size	“16”
N-acetyl-L-leucine first	“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.”
Placebo first	“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.”

“This 2 × 2 crossover, double-blind, randomized clinical trial was conducted on 20 patients with AT.” (opens the source at this quote in a new tab)

Availability of the statistical analysis plan

Document	Registry sharing plan
Statistical analysis plan	“No - There is not a plan to make this available”
Study protocol	“Yes - There is a plan to make this available”

Exclusions before randomization

“After excluding four patients, 16 subjects (eight females, eight males; mean age 9.8 ± 3.5 years) with a definitive genetic diagnosis of AT were randomly assigned to one of two study groups, with one group receiving 1-4 g/day NALL or a placebo for six weeks.” (opens the source at this quote in a new tab)

Sex and age of the randomized participants

Characteristic	Value
Participants randomized	“16 subjects”
Sex	“eight females, eight males”
Age	“mean age 9.8 ± 3.5 years”

Ataxia outcomes

“Although patients' nausea and constipation were improved, the results failed to reveal any significant benefits of NALL treatment on ataxia symptoms.” (opens the source at this quote in a new tab)
“NALL treatment had no significant effects on SARA, SCAFI-9HPT (9-hole peg test) nondominant, SCAFI-9HPT dominant, or SCAFI-8WMT (8 m walking time) (p > 0.05).” (opens the source at this quote in a new tab)

Dietary intake

“Furthermore, there were no significant changes in energy and macronutrient intake after NALL treatment.” (opens the source at this quote in a new tab)

Authors' conclusion

“To the best of our knowledge, this was the first placebo-controlled, randomized clinical trial exploring NALL's potential effects for treating AT.” (opens the source at this quote in a new tab)
“Despite improvements in some symptomss, NALL intervention failed to improve motor function significantly.” (opens the source at this quote in a new tab)

PedsQL physical health score

“Quality of life (QOL) was evaluated by a specialist using the PedsQL questionnaire.” (opens the source at this quote in a new tab)
“Our patient's Physical Health score in Child self-report and Parent proxy-report did not significantly change in the treatment group compared to the placebo (p > 0.05).” (opens the source at this quote in a new tab)

Safety assessment and reported side effects

“Fasting blood samples were taken from all subjects before and after each intervention to determine potential side effects.” (opens the source at this quote in a new tab)
“None of the volunteers reported serious or moderate side effects.” (opens the source at this quote in a new tab)

Gastrointestinal symptoms

“However, patients' nausea and constipation were improved by NALL, which can be a relevant benefit clinically.” (opens the source at this quote in a new tab)

Summary

The trial randomized 16 participants at one hospital after 4 of 20 were excluded, with 6-week treatment periods separated by a 4-week washout. The participants had a mean age of 9.8 years. The abstract reports the comparisons with placebo as p > 0.05 and gives no effect estimates, confidence intervals, or scores by period. The registry names Hubei ipure Biotech as the source of the N-acetyl-L-leucine caplets, dosed at 1 to 4 g per day by weight, and states that no statistical analysis plan will be shared. A 2026 systematic review rated the trial as having “some concerns” on the RoB 2 tool and listed limited duration and a potential carry-over effect as its limitations. The evidence quoted here comes from the article's abstract and the registry record.

Risk of bias assessment in a systematic review

Item	Assessment
Risk of bias (RoB 2)	“Some concerns”
Limitations	“Limited duration; potential carry‐over effect”

“The primary sources of concern in these trials related to potential deviations from intended interventions and incomplete reporting of randomization procedures.” (opens the source at this quote in a new tab)