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| Name | Class |
|---|---|
| Families of Spinal Muscular Atrophy | OTHER |
| Leadiant Biosciences, Inc. | INDUSTRY |
| Abbott | INDUSTRY |
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This is a multi-center trial to assess safety and efficacy of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Outcome measures will include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.
This is a multi-center phase II trial of a combined regimen of oral valproic acid (VPA) and carnitine in patients with Spinal Muscular Atrophy (SMA) 2 to 17 years of age. Cohort 1 is a double-blind placebo-controlled randomized intention to treat protocol for SMA "sitters" 2 - 8 years of age. Subjects will undergo two baseline assessments over 4 to 6 week period, then will be randomized to treatment or placebo for the next six months. All subjects will then be placed on active treatment for the subsequent six month period. Cohort 2 is an open label protocol for SMA "standers and walkers" 3 - 17 years of age to explore responsiveness of efficacy outcomes. Subjects will undergo two baseline assessments over a four to six week period, followed by one year active treatment with VPA and carnitine. Outcome measures are performed every 3 to 6 months, and include blood chemistries, functional testing, pulmonary function testing, electrophysiological evaluations, PedsQL quality of life assessment, quantitative assessments of survival motor neuron (SMN) mRNA from blood samples, growth and vital sign parameters. Six centers will enroll a total of 90 patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1a | Placebo Comparator | Patients in Cohort 1a - Placebo Comparator, will be on a placebo for 6 months and then will switch to the active treatment. Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor or equivalent placebo in the liquid form. |
|
| Cohort 1b | Active Comparator | Cohort 1b - Active Comparator will be on treatment throughout the study. Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form. |
|
| Cohort 2 | Experimental | Cohort 2 pts are on open-label treatment throughout. Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor or equivalent placebo in the liquid form. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Valproic Acid and Levocarnitine | Drug | VPA,sprinkle cap; Levocarnitine, syrup; dosage is by weight |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety Labs | Participants will have labs drawn regularly to maintain appropriate dosing and monitor liver function | -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs |
| Efficacy, Measured Through Motor Function Assessments | -4wks, 0, 3 mo, 6 mo, 12 mo | |
| Modified Hammersmith Change From Baseline to 6 Months | Comparison of Modified Hammersmith Change from baseline to 6 months. Scores range from 0 to 40. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of non-ambulant children with SMA in multiple research trials as well as in clinical settings. | 0 months, 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Quantitative Assessment of SMN mRNA From Blood Samples | -4wks or 0, 3 mo, 6 mo, 12 mo | |
| Peds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs) | -4wks, 0, 3mo, 6mo, 12mo | |
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Inclusion Criteria:
Cohort 1
Cohort 2
Exclusion Criteria:
Cohort 1
Cohort 2
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| Name | Affiliation | Role |
|---|---|---|
| Kathryn J Swoboda, M.D. | University of Utah/Primary Children's Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Baltimore | Maryland | 21287 | United States | ||
| Children's Hospital of Michigan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8912176 | Background | Brahe C, Bertini E. Spinal muscular atrophies: recent insights and impact on molecular diagnosis. J Mol Med (Berl). 1996 Oct;74(10):555-62. doi: 10.1007/s001090050059. | |
| 4245389 | Background | Roberts DF, Chavez J, Court SD. The genetic component in child mortality. Arch Dis Child. 1970 Feb;45(239):33-8. doi: 10.1136/adc.45.239.33. |
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Subject's were recruited during the periods of September 2005 to September 2006 across the United States.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1a Sitters Placebo Then Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor or equivalent placebo in the liquid form. |
| FG001 | Cohort 1b Sitters Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form. |
| FG002 | Cohort 2 Standers and Walkers - Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1a Sitters Placebo Then Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor or equivalent placebo in the liquid form. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety Labs | Participants will have labs drawn regularly to maintain appropriate dosing and monitor liver function | Not Posted | -4 wks, 0, 2 wks, 3 mo, 6 mo, 9 mo, 12 mo for safety labs; throughout for AEs | Participants | |||||||||||
| Primary | Efficacy, Measured Through Motor Function Assessments | Not Posted | -4wks, 0, 3 mo, 6 mo, 12 mo | Participants |
Phase 1 Serious Adverse Events (time period during which placebo (1a) and treatment (1b)were randomly treated): 6 months. And Phase 1 and 2 Adverse Events: 12 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1a Sitters Placebo Then Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor or equivalent placebo in the liquid form. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain Upper | Gastrointestinal disorders |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sandra Reyna, M.D. | University of Utah | 801-581-3551 | sreyna@genetics.utah.edu |
Not provided
| ID | Term |
|---|---|
| D009134 | Muscular Atrophy, Spinal |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
Not provided
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| ID | Term |
|---|---|
| D014635 | Valproic Acid |
| D002331 | Carnitine |
| ID | Term |
|---|---|
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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| Placebo | Drug |
|
| Max CMAP Amplitude (Mean) |
The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed. |
| 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
| Max CMAP Amplitude Median | The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed. | 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
| Ulnar MUNE | -4 wks, 0, 3 mo, 6 mo, 12 mo |
| Growth and Vital Sign Parameters | -4 wks, 0, 3mo, 6mo, 12mo |
| Nutritional Status | -4 wks, 0, 3mo, 6mo, 12mo |
| DEXA | 0, 6mo, 12mo |
| Max CMAP Area (Mean) | The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve. | 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
| Max CMAP Area (Median) | The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve. | 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
| Detroit |
| Michigan |
| 48201 |
| United States |
| Ohio State University | Columbus | Ohio | 43210-1228 | United States |
| University of Utah/Primary Children's Medical Center | Salt Lake City | Utah | 84132 | United States |
| University of Wisconsin Children's Hospital | Madison | Wisconsin | 53792-9988 | United States |
| Hospital Sainte-Justine | Montreal | Quebec | H3T 1C5 | Canada |
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| 8614490 | Background | Crawford TO. From enigmatic to problematic: the new molecular genetics of childhood spinal muscular atrophy. Neurology. 1996 Feb;46(2):335-40. doi: 10.1212/wnl.46.2.335. No abstract available. |
| 1972783 | Background | Gilliam TC, Brzustowicz LM, Castilla LH, Lehner T, Penchaszadeh GK, Daniels RJ, Byth BC, Knowles J, Hislop JE, Shapira Y, et al. Genetic homogeneity between acute and chronic forms of spinal muscular atrophy. Nature. 1990 Jun 28;345(6278):823-5. doi: 10.1038/345823a0. |
| 7910982 | Background | Melki J, Lefebvre S, Burglen L, Burlet P, Clermont O, Millasseau P, Reboullet S, Benichou B, Zeviani M, Le Paslier D, et al. De novo and inherited deletions of the 5q13 region in spinal muscular atrophies. Science. 1994 Jun 3;264(5164):1474-7. doi: 10.1126/science.7910982. |
| 10369862 | Background | Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, McPherson JD. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999 Jul;8(7):1177-83. doi: 10.1093/hmg/8.7.1177. |
| 9245983 | Background | Campbell L, Potter A, Ignatius J, Dubowitz V, Davies K. Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype. Am J Hum Genet. 1997 Jul;61(1):40-50. doi: 10.1086/513886. |
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| 10655541 | Background | Monani UR, Sendtner M, Coovert DD, Parsons DW, Andreassi C, Le TT, Jablonka S, Schrank B, Rossoll W, Prior TW, Morris GE, Burghes AH. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet. 2000 Feb 12;9(3):333-9. doi: 10.1093/hmg/9.3.333. |
| 11791208 | Background | Feldkotter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. 2002 Feb;70(2):358-68. doi: 10.1086/338627. Epub 2001 Dec 21. |
| 11839954 | Background | Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AH, Prior TW. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002 Jan-Feb;4(1):20-6. doi: 10.1097/00125817-200201000-00004. |
| 9323130 | Background | Fischer U, Liu Q, Dreyfuss G. The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell. 1997 Sep 19;90(6):1023-9. doi: 10.1016/s0092-8674(00)80368-2. |
| 11504946 | Background | Chang JG, Hsieh-Li HM, Jong YJ, Wang NM, Tsai CH, Li H. Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9808-13. doi: 10.1073/pnas.171105098. |
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| Background | Lindstedt S, Lindstedt G. Distribution and Excretion of Carnitine in the Rat. Acta. Chem. Scand. 1961;15:701-702 |
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| Background | Scriver C, Beautet A, Sly W, Valle D. The Metabolic Basis of Inherited Disease. New York: McGraw Hill, 1989 |
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| 21754985 | Derived | Kissel JT, Scott CB, Reyna SP, Crawford TO, Simard LR, Krosschell KJ, Acsadi G, Elsheik B, Schroth MK, D'Anjou G, LaSalle B, Prior TW, Sorenson S, Maczulski JA, Bromberg MB, Chan GM, Swoboda KJ; Project Cure Spinal Muscular Atrophy Investigators' Network. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy. PLoS One. 2011;6(7):e21296. doi: 10.1371/journal.pone.0021296. Epub 2011 Jul 6. |
| 20808854 | Derived | Swoboda KJ, Scott CB, Crawford TO, Simard LR, Reyna SP, Krosschell KJ, Acsadi G, Elsheik B, Schroth MK, D'Anjou G, LaSalle B, Prior TW, Sorenson SL, Maczulski JA, Bromberg MB, Chan GM, Kissel JT; Project Cure Spinal Muscular Atrophy Investigators Network. SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy. PLoS One. 2010 Aug 19;5(8):e12140. doi: 10.1371/journal.pone.0012140. |
| Excessive weight gain |
|
| BG001 | Cohort 1b Sitters Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form. |
| BG002 | Cohort 2 Standers and Walkers - Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Secondary | Quantitative Assessment of SMN mRNA From Blood Samples | Not Posted | -4wks or 0, 3 mo, 6 mo, 12 mo | Participants |
| Secondary | Peds QL™ Assessment: Parental Version (All), Child Versions (> 5yrs) | Not Posted | -4wks, 0, 3mo, 6mo, 12mo | Participants |
| Secondary | Max CMAP Amplitude (Mean) | The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed. | Posted | Mean | Standard Deviation | mV | 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
|
|
|
| Secondary | Max CMAP Amplitude Median | The maximum Compound Motor Action Potential (CMAP) is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This is done multiple times, the outcome used is the highest peak, or response observed. | Posted | Median | Full Range | mV | 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
|
|
|
| Secondary | Ulnar MUNE | Not Posted | -4 wks, 0, 3 mo, 6 mo, 12 mo | Participants |
| Secondary | Growth and Vital Sign Parameters | Not Posted | -4 wks, 0, 3mo, 6mo, 12mo | Participants |
| Secondary | Nutritional Status | Not Posted | -4 wks, 0, 3mo, 6mo, 12mo | Participants |
| Post-Hoc | Modified Hammersmith Extend Baseline | Baseline Modified Hammersmith Extend testing. The baseline test is the score they receive during their screening visits. This scale ranges from 0 to 56. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of children with SMA in multiple research trials as well as in clinical settings. | Analysis was determined per protocol | Posted | Mean | Full Range | Score | 1 month prior to enrollment, at enrollment (0 months) |
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| Primary | Modified Hammersmith Change From Baseline to 6 Months | Comparison of Modified Hammersmith Change from baseline to 6 months. Scores range from 0 to 40. A higher score indicates a better outcome. This scale is used to assess gross motor abilities of non-ambulant children with SMA in multiple research trials as well as in clinical settings. | Analysis only pertains to cohort 1a and 1b. | Posted | Mean | Standard Deviation | Score | 0 months, 6 months |
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| Secondary | DEXA | Not Posted | 0, 6mo, 12mo | Participants |
| Secondary | Max CMAP Area (Mean) | The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve. | Posted | Mean | Standard Deviation | mVms | 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
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| Secondary | Max CMAP Area (Median) | The maximum Compound Motor Action Potential (CMAP) area is a measurement obtained through EMG testing that is associated with disease progression. In this study, we measure the maximum CMAP by stimulating one nerve in the hand and measuring the response of the muscle. This procedure is repeated multiple times. The maximum area is the response that results in the largest area under the response curve. | Posted | Median | Full Range | mVms | 1 month prior to official enrollment, beginning of study (0 months), 6 months, 12 months (data point not available) |
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| 1 |
| 31 |
| 18 |
| 31 |
| EG001 | Cohort 1b Sitters Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form. | 4 | 30 | 23 | 30 |
| EG002 | Cohort 2 Standers and Walkers - Treatment | Dosage of the VPA will start at 10-20 mg/kg/day divided into two or tree doses. The dose will be adjusted to achieve a therapeutic trough level of 50-120 micrograms/ml. VPA will be given in the form of 125 mg sprinkle capsules. Dosage for Carnitor will be 50 mg/kg/day with a maximum dose of 10000 mg/day divided into two doses. Carnitor elixir comes as 500 mg/5 ml. All subjects will be given Carnitor in the liquid form. | 4 | 33 | 28 | 33 |
| Dehydration | Metabolism and nutrition disorders |
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| Diarrhea | Gastrointestinal disorders |
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| General Disorder | General disorders | Pyrexia |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders |
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| Pneumonitis | Infections and infestations |
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| Skin Rash | Skin and subcutaneous tissue disorders |
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| Tachyponea | Respiratory, thoracic and mediastinal disorders |
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| Upper respiratory infection | Infections and infestations |
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| Vomiting | Gastrointestinal disorders |
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| Agitation | Nervous system disorders |
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| Arthralgia | Musculoskeletal and connective tissue disorders |
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| Bronchitis | Infections and infestations |
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| Chocking Sensation | Respiratory, thoracic and mediastinal disorders |
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| Constipation | Gastrointestinal disorders |
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| Cough | Respiratory, thoracic and mediastinal disorders |
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| Croup | Infections and infestations |
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| Decreased Appetite | Metabolism and nutrition disorders |
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| Dehydration | Metabolism and nutrition disorders |
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| Dermatitis Allergic | Immune system disorders |
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| Diarrhea | Gastrointestinal disorders |
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| Dry Mouth | Gastrointestinal disorders |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders |
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| Ear Infection | Infections and infestations |
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| Emotional Disorder of Childhood | Psychiatric disorders |
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| Fatigue | General disorders |
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| Femur Fracture | Musculoskeletal and connective tissue disorders |
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| Foot Fracture | Musculoskeletal and connective tissue disorders |
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| Forearm Fracture | Musculoskeletal and connective tissue disorders |
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| Gastroesophagheal Reflux Disease | Gastrointestinal disorders |
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| Hand Fracture | Musculoskeletal and connective tissue disorders |
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| Headache | Nervous system disorders |
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| Hypersensitivity | Immune system disorders |
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| Impulsive Behaviour | Nervous system disorders |
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| Incontinence | Renal and urinary disorders |
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| Increased Appetite | Metabolism and nutrition disorders |
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| Increased Urination Frequency | Renal and urinary disorders |
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| Irritability | Nervous system disorders |
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| Join Sprain | Injury, poisoning and procedural complications |
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| Joint Pain | Musculoskeletal and connective tissue disorders |
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| Lethargy | Nervous system disorders |
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| Multiple Allergies | Immune system disorders |
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| Muscle Cramp | Musculoskeletal and connective tissue disorders |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders |
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| Nasopharyngitis | Infections and infestations |
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| Nausea | Gastrointestinal disorders |
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| Otorrhoea | Ear and labyrinth disorders |
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| Oxygen Saturation Decreased | Investigations |
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| Pain in Extremity | Musculoskeletal and connective tissue disorders |
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| Patella Fracture | Musculoskeletal and connective tissue disorders |
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| Pharyngeal Pain | Respiratory, thoracic and mediastinal disorders |
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| Pharyngeal Pain | Respiratory, thoracic and mediastinal disorders |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders |
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| Pneumonitis | Infections and infestations |
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| Pyrexia | General disorders |
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| Rash Papular | Skin and subcutaneous tissue disorders |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders |
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| Sinusitis | Infections and infestations |
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| Tachypnoea | Respiratory, thoracic and mediastinal disorders |
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| Tinea Infection | Infections and infestations |
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| Tremor | Nervous system disorders |
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| Upper Respiratory Infection | Infections and infestations |
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| Urinary Tract Infection | Infections and infestations |
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| Vomiting | Gastrointestinal disorders |
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| Weight Incresed | Investigations |
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Not provided
Not provided
| D019636 | Neurodegenerative Diseases |
| D009468 | Neuromuscular Diseases |
| D009930 |
| Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
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| Change from Baseline |
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