Fragile X Tremor/Ataxia Syndrome
Conditions
Brief summary
The objective of this study is to determine if citocoline is effective for balance abnormalities and to stabilize cognitive decline in patients with fragile X-associated tremor ataxia syndrome. The study will test 1000mg twice daily of citocoline for 12 months in an open label pilot study, with study visits at baseline, 3, 6, and 12 months.
Detailed description
The purpose of this study was to determine if citicoline was safe for the treatment of tremor and balance abnormalities and to stabilize cognitive decline in patients with fragile X-associated tremor ataxia syndrome. Ten participants with diagnosed FXTAS were administered 1000 mg of citicoline once daily for 12 months. Outcome measures and neurological examination were performed at baseline, 3 months, 6 months, and 12 months. The primary outcome was safety. Secondary outcomes included change in FXTAS Rating Scale score, a battery of neuropsychological tests, an instrumented Timed up and go test, computerized dynamic posturography, 9-hole pegboard test, and balance confidence and psychiatric symptom questionnaires.
Interventions
DRUGcitocoline
Ten subjects will receive 1,000mg once daily of citicoline. Each subject will stay on the study drug for 12 months. The outcome measures will be assessed at baseline and then again at the end of month 3, month 6, and month 12. The subjects will continue taking the same study drug at the same dose throughout the entire trial.
Sponsors
Rush University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of FXTAS * Serum creatine kinase, complete metabolic panel, complete blood count, liver function tests, renal function tests, platelets and EKG are within normal limits
Exclusion criteria
* Legal incapacity or limited legal capacity * Presence of severe renal disease (BUN 50% greater than normal or creatinine clearance \<60 mL/min) or hepatic disease. * Abnormal creatine kinase and/or platelet count in the past 6 months (as determined by lab reports obtained from primary care physicians or conducted at baseline). * Women of childbearing potential who are pregnant at the time of screening or who will not use adequate protection during participation of the study. * Allergy/sensitivity to the drug of its formulations. * Concurrent participation in another clinical study. * Active substance use or dependence. * Serious illness (requiring systematic treatment/or hospitalization) until the subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 60 days prior to study entry. * Inability or unwillingness of the subject or legal guardian/representative to give written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FXTAS Rating Scale Score | 12 months | The FXTAS Rating Scale (FXTAS-RS), which was designed to measure the severity of motor signs in FXTAS patients, was administered to each participant. The FXTAS-RS was designed to measure the severity of motor signs of FXTAS, tremor, ataxia, and parkinsonism. The scale was developed from a combination of three separate measures: the Clinical Rating Scale for Tremor (CRST), the International Cooperative Ataxia Rating Scale (ICARS), and the Unified Parkinson's Disease Rating Scale (UPDRS). The resultant scale has 44 items and a possible total score of 0-226. A higher score indicates worse symptoms. For this study, improvement was defined as a 20% improvement on the FXTAS-RS. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Citocoline All participants were white and non-Hispanic; there were nine men and one woman. This distribution is expected as there is a lower penetrance of FXTAS in women from X-inactivation. The subject with probable FXTAS was also the female subject. Nine participants completed the one-year follow-up and one participant with a low platelet count withdrew prior to the end of the study and outcome data was missing for this participant at 12 months, but all available data were used for analysis. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Citocoline |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 70 years STANDARD_DEVIATION 7.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States East Coast | 1 Participants |
| Region of Enrollment United States Midwestern | 9 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 5 / 10 |
| serious Total, serious adverse events | 6 / 10 |
Outcome results
Primary
FXTAS Rating Scale Score
The FXTAS Rating Scale (FXTAS-RS), which was designed to measure the severity of motor signs in FXTAS patients, was administered to each participant. The FXTAS-RS was designed to measure the severity of motor signs of FXTAS, tremor, ataxia, and parkinsonism. The scale was developed from a combination of three separate measures: the Clinical Rating Scale for Tremor (CRST), the International Cooperative Ataxia Rating Scale (ICARS), and the Unified Parkinson's Disease Rating Scale (UPDRS). The resultant scale has 44 items and a possible total score of 0-226. A higher score indicates worse symptoms. For this study, improvement was defined as a 20% improvement on the FXTAS-RS.
Time frame: 12 months
Population: 9 patients with FXTAS who participated in the study for 12 months were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Citocoline | FXTAS Rating Scale Score | 45.8 score on a scale | Standard Deviation 21.22 |