Autism, Childhood Apraxia of Speech, Verbal Apraxia
Conditions
Brief summary
This is a 20-week study for children between 3 and 6 years old with confirmed childhood apraxia of speech (CAS). The study includes a 12-week open-label pilot feasibility study of an investigational drug (Omega-DEK) plus L-carnitine (Carnitor®), which is followed by an 8-week randomized, placebo-controlled discontinuation period among the same study participants.
Detailed description
Verbal apraxia (VA) is a severe neurological motor planning speech disorder of unknown etiology. It is a devastating disorder that is insufficiently recognized by general pediatricians and often goes unaddressed and improperly treated during critical years of speech and language development. The high prevalence of this disorder excludes it as an "orphan" disease, although like autism, it may have met the definition over a decade ago. However, inadequate awareness of this condition among practitioners renders it a neglected disorder. Confusion around this condition is reflected by the vast number of terms used to define it, including Childhood Apraxia of Speech, Developmental Apraxia, Developmental Dyspraxia, Speech Apraxia, and Speech Dyspraxia to name a few. Approximately half of children with autism spectrum disorders (ASD) have some degree of apraxia, although not all apraxic children are autistic. There is currently no recognized cure for VA, and it is thought to be a life-long condition. Standard treatment is extremely costly and involves intensive and frequent 1:1 speech therapy with a speech pathologist knowledgeable in VA. Typical response to therapy tends to be slow, and some children do not learn how to talk, thereby requiring alternate means of communication. Children with this disorder find it very difficult to correctly pronounce sounds, syllables, and words, despite intense effort. Intelligibility is poor, and some children remain completely speechless and require the use of augmentative communication devices, sign language and/or a picture exchange communication system. Many children with VA present with a unique but homogeneous group of neurological symptoms that affect coordination, muscle tone and sensory issues in addition to expressive speech delay, suggesting a common underlying mechanism of disease. Vitamin E (vit E) deficiency causes a constellation of symptoms that overlap those of speech apraxia, limb dyspraxia, hypotonia and sensory integration dysfunction (including abnormalities in proprioception, vestibular sensation, and pain interpretation) that often occur in VA and ASD. Low bioavailability of vit E will create an environment within the cell membrane where vital polyunsaturated fatty acids (PUFAs) are vulnerable to lipid peroxidation and early destruction. This can lead to a functional PUFA deficiency and neurological sequelae that may be reversible through supplementation with PUFA/vit E. In addition, PUFA supplementation increases utilization of vit E in the body. These two supplements may have synergistic effects at higher doses. An unexpected number of apraxic children have a carnitine deficiency, high antigliadin antibodies and carry a gluten-sensitivity major histocompatibility complex (HLA), suggesting abnormal fatty acid metabolism, increased oxidative stress and a potential link to gastrointestinal inflammation and gluten-sensitivity that creates a distinctive nutritional requirement in these children that may benefit from an investigational drug specifically formulated to targets unique deficiencies that contribute to VA. The researchers speculate that patients with gluten sensitivity or those carrying a celiac HLA with autism/VA may not have classic celiac disease, but perhaps a broader diagnosis of gluten-sensitivity associated with malabsorption and neurobehavioral consequences of nutritional deficiencies that needs consideration. The less sensitive celiac biomarker, antigliadin immunoglobulin G (IgG), frequently found in both ASD and VA may represent a biomarker that identifies an intervention-responder group. A recent double-blind randomized, placebo-controlled trial in irritable bowel syndrome concluded that a non-celiac gluten intolerance my exist, a concept in need of exploration in both ASD and VA. In this study, children between 3 and 6 years old with confirmed childhood apraxia of speech (CAS) will take an investigational drug (Omega-DEK) plus L-carnitine (Carnitor®) for 12 weeks. This open-label period of the study is followed by an 8-week blinded trial where participants will be randomized to continue taking Omega-DEK or to take a placebo. Additionally, 10 participants will be enrolled in a cohort with expanded follow-up to examine the feasibility of conducting a 12-month open-label trial of Omega-DEK plus L-carnitine in participants aged ≥2 years who have a working diagnosis of CAS, intestinal lymphangiectasia, or fat malabsorption syndrome (in isolation or associated with other medical conditions such as cystic fibrosis, celiac disease, etc.).
Interventions
DRUGOmega-DEK
Participants take 2 capsules, twice daily (BID).
DRUGL-carnitine
Participants take 250 mg L-carnitine administered as a 2.5 mL oral solution twice daily (BID).
DRUGPlacebo
A placebo of palm kernel oil to match Omega-DEK is provided. Participants take 2 capsules, twice daily (BID).
Sponsors
Claudia R. Morris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This study has a 12-week open-label trial of Omega-DEK plus L-carnitine followed by an 8-week placebo-controlled discontinuation where participants are randomized to continue Omega-DEK or take a placebo. A third study arm is for an open-label trial with a cohort of 10 participants taking Omega-DEK plus L-carnitine and have expanded follow-up of 12 months.
Eligibility
Sex/Gender
ALL
Age
36 Months to 6 Years
Healthy volunteers
No
Inclusion criteria
for Main Trial: 1. Confirmed diagnosis of childhood apraxia of speech/verbal apraxia by a qualified professional (SLP) based on established guidelines 2. Male and female, age 36 months - 6 years (inclusive) 3. Ability to comprehend and use Standard American English
Exclusion criteria
for Main Trial: 1. Children unable to tolerate oral supplementation 2. Known allergy to fish oil, palm kernel oil or other ingredients in investigational drug 3. Medical or genetic condition that in the opinion of the PI/Co-Is may affect participation and compromise results (including significant receptive language delay, moderate-severe cognitive delay, complex medical history, hearing loss, cerebral palsy, history of traumatic brain injury or severe anoxic event, Down's syndrome) 4. Known seizure disorder or history of febrile seizures 5. History of cardiac dysrhythmia or abnormal ECG at baseline 6. A prothrombin time test with an international normalised ratio (PT/INR) \>1.2 7. Use of blood thinners, including chronic aspirin, chronic NSAIDS, warfarin etc. 8. A history of PUFA or vit E supplementation use within 3 months prior to enrollment in the study 9. On an elimination diet for \< 3 months (gluten, casein, yeast free etc.) prior to enrollment, or planning to initiate a special diet during the study 10. Recent reintroduction of food items from elimination diet \< 3 months 11. On any additional nutritional interventions/supplements \< 3 months (i.e. high dose vitamins/minerals that exceed what would be found in a children's multivitamin supplement etc., probiotics) 12. Any new chronic medication \< 3 months prior to enrollment (stable doses \> 3 months allowed; medications for acute illness allowed including antipyretics, antibiotics, asthma medication) 13. Anticipated initiation of new chronic medication during study timeline including new attention-deficit/hyperactivity disorder (ADHD) medications, other behavior medications 14. Plans to try additional complementary interventions or diets during the study period 15. Planned surgery during or within 4 weeks after conclusion of trial Inclusion Criteria for Expanded Cohort: 1. Working Diagnosis of CAS, or intestinal lymphangiectasia, or fat malabsorption syndrome (in isolation or associated with other medical conditions such as cystic fibrosis, celiac disease, etc.) 2. Male and female, aged ≥2 years 3. Ability to comprehend and use Standard American English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Retained in Study | Up to Week 20 | Feasibility of the intervention is assessed with the percentage of enrolled participants who complete the 20 week study. Successful retention is defined as \>85% of enrolled participants completing the study. |
| Percent of Expanded Cohort Recruited | Up to Month 12 | Feasibility of conducting a 12-month, open-label trial is measured by successful recruitment, which is defined as \<20% refusal of eligible children. |
| Percent of Expanded Cohort Retained | Up to Month 12 | Feasibility of conducting a 12-month, open-label trial is measured by successful retention, which is defined as \>85% of study participants completing the study. |
| Percent of Expanded Cohort Complying with Treatment Regimen | Up to Month 12 | Feasibility of conducting a 12-month, open-label trial is measured by successful compliance, which is defined as \>75% of participants with compliance with the treatment regimen. |
| Percent of Expanded Cohort With Complete Data | Up to Month 12 | Feasibility of conducting a 12-month, open-label trial is measured by collection of study data, which is defined as \>90% of participants providing outcome data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Complete Outcome Data | Up to Week 20 | Feasibility of the intervention is assessed with the percentage of participants who complete all surveys and study visits. Successful collection of outcome data is defined as \>90% of participants completing study surveys and visits. |
| Change in Dynamic Evaluation of Motor Speech Skill (DEMSS) Score | Baseline, Week 12, Week 20 | The Dynamic Evaluation of Motor Speech Skill (DEMSS) is a validated tool specifically designed to identify the level of breakdown in a child's ability to speak so that treatment can be established, and improvement tracked. The DEMSS is comprised of 9 subtests with a total of 66 utterances which are associated with 171 items. Four subscores for overall articulatory accuracy of the word, vowel accuracy, prosodic accuracy, and consistency, are calculated. An overall score is calculated and ranges from 0 to 426, where lower scores suggest that CAS is present. Within a clinical setting, scores between 0 and 323 indicate CAS, scores between 323 and 373 indicate mild evidence of mild CAS, and scores of 373 to 426 indicate little or no evidence of CAS. Baseline scores are compared to scores at Week 12, for analysis of the open-label portion of the study, while Week 12 and Week 20 scores are compared for analysis of the randomized discontinuation portion of the study. |
| Mean Length of Utterances (MLU) | Baseline, Week 12, Week 20 | Mean length of utterance (MLU) is an assessment of expressive language measures the average number of morphemes per utterance. Morphemes are smallest language elements that make up linguistic expression. A spontaneous speech sample will be obtained and MLU is calculated as the number of morphemes in each utterance divided by the total number of utterances. |
| Clinical Global Impression for Improvement Scale (CGI-I) Score | Weeks 1, 4, 8, 12 (during the open-label portion of the study), weekly during Weeks 13-22 (during the randomized portion of the study) | The CGI-I is a 7-point scale designed to measure overall improvement from baseline. The CGI-I is rated by an independent evaluator who is blind to treatment assignment during the randomized discontinuation phase. Scores range from 1 (Very Much Improved) to 4 (Unchanged) to 7 (Very Much Worse). Positive response to treatment (an improvement from baseline) is defined by a rating of Much Improved or Very Much Improved. Scores of 3 (minimally improved), 4 (no change) and 5 (minimally worse) indicate no change. Scores of 6 or 7 are considered as a worsening of symptoms from baseline (a negative response). |
Countries
United States
Contacts
CONTACTClaudia R Morris, MD
PRINCIPAL_INVESTIGATORClaudia R Morris, MD
Emory University
PRINCIPAL_INVESTIGATORLawrence Scahill, MSN,PhD
Emory University
Outcome results
None listed