Publications by authors named "Steve B Ampah"

9 Publications

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Long-term safety and efficacy of highly purified cannabidiol for treatment refractory epilepsy.

Epilepsy Behav 2021 04 2;117:107862. Epub 2021 Mar 2.

Department of Neurology and the UAB Epilepsy Center, University of Alabama at Birmingham, Birmingham, AL, USA.

Objective: To evaluate the safety, efficacy, and tolerability of highly purified cannabidiol (CBD) for the treatment of seizures in children and adults with treatment-resistant epilepsy (TRE) in an open-label, expanded access program (EAP).

Methods: One hundred sixty-nine participants (89 children and 80 adults) with TRE received plant-derived highly purified CBD (Epidiolex® in the U.S.; 100 mg/mL oral solution) with a starting dose of 5 mg/kg/day divided twice per day and titrated to a maximum dose of 50 mg/kg/day over the study period to seizure control and tolerability and followed for up to 2 years. Seizure frequency (calendars) and severity (Chalfont Seizure Severity Score; CSSS) were collected at every study visit. Adverse Events were reported at/between study visits as required, and participants also completed Adverse Events Profile (AEP) which generates a numerical representation of AEs. Response to CBD was defined as ≥50% reduction in seizure frequency. Given non-normal distribution of seizure frequency, a log transformation was applied after which the generalized least squares regression model for longitudinal data was used.

Results: Evidence from the adjusted model revealed a significant mean reduction in seizure frequency compared to baseline in children and adults at all time points (1 month and 1 and 2 years). Percentage of children achieving ≥50% seizure frequency reduction was 44% at month 1, and 41% at year 1, and 61% reduction at year 2, while adult responder rates were 34% at month 1, 53% at year 1, and 71% at year 2 (all P < 0.0001). CSSS showed a sustained reduction from baseline to all 3 time points. Children displayed 52% seizure reduction at month 1, a 51% reduction at year 1, and 75% reduction at year 2. Seizure reductions in adults were 60%, 81%, and 85%, respectively (all P < 0.0001). While there were no significant differences between seizure frequency reduction between children and adults at all time points, there was a significant difference in seizure severity reduction at year 1, with adults reporting greater improvement in seizure severity (P < 0.001). The most commonly reported adverse events in the study period were diarrhea, sedation, and decreased appetite. AEP revealed significant improvement from baseline at multiple time points in adults and children, and the mean AEP scores were always lower compared to baseline over the duration of the study.

Significance: Our study provides further evidence of sustained seizure frequency and severity reduction over two years of treatment with highly purified CBD in TRE. In addition, CBD was generally well tolerated with minority of participants experiencing adverse events resulting in stopping CBD.
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http://dx.doi.org/10.1016/j.yebeh.2021.107862DOI Listing
April 2021

Cognitive function and adaptive skills after a one-year trial of cannabidiol (CBD) in a pediatric sample with treatment-resistant epilepsy.

Epilepsy Behav 2020 10 29;111:107299. Epub 2020 Jul 29.

University of Alabama at Birmingham, Department of Neurology, 1720 7th Avenue South, Birmingham, AL 35233, USA.

Objective: Cannabidiol (CBD) is a nonpsychoactive derivative of cannabis. Studies indicate that it is safe and effective in treating certain types of epilepsy. The present study examined the presence of adverse or beneficial cognitive or functional adaptive effects associated with CBD in the treatment of children, adolescents, and teenagers with treatment-resistant epilepsy (TRE) as part of an ongoing prospective, open-label safety study.

Methods: Participants (N = 38) between the age of 3 and 19 years with TRE were enrolled in an open-label study of a pharmaceutical formulation of CBD (Epidiolex®; GW Research Ltd.) as an add-on treatment. In addition to baseline physical, neurological, and laboratory testing, cognitive assessment was completed prior to initiating CBD and after one year, both using the NIH Toolbox Cognition Battery (NIHTB-CB). Many participants were unable to complete the NIHTB-CB because of the magnitude of their cognitive impairment (n = 24), and in these cases, the participant's caregiver was asked to complete the Adaptive Behavior Assessment System - Second Edition (ABAS-II) as a measure of functional adaptive skills.

Results: There were no statistically significant changes in cognitive function, as measured by the NIHTB-CB, in those participants who were able to complete such testing, but there was a nonsignificant trend toward improvement in some cognitive domains. For participants who were unable to complete formal standardized cognitive testing because of the magnitude of their cognitive impairment, their functional adaptive skills, as measured by the ABAS-II, were unchanged after a one-year trial of CBD.

Significance: Our findings suggest that CBD, as an add-on drug for TRE in a pediatric sample, does not appear to cause adverse effects (AEs) involving cognition or adaptive function over one year of treatment.
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http://dx.doi.org/10.1016/j.yebeh.2020.107299DOI Listing
October 2020

Drug-drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program.

Epilepsy Behav 2019 09 2;98(Pt A):201-206. Epub 2019 Aug 2.

Department of Neurology, Division of Epilepsy, University of Alabama at Birmingham, Birmingham, AL, USA.

Objective: We have previously shown that cannabidiol (CBD; Epidiolex®) significantly affects levels of clobazam/N-desmethylclobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine. In the present study, we tested whether the presence of concomitant clobazam affected seizure frequency and severity (treatment response) 12 weeks after initiation of therapy with CBD in patients with treatment-resistant epilepsy (TRE). The secondary questions were whether the presence of any of the other antiepileptic drugs (AEDs) had an effect on seizure frequency or severity at 12, 24, or 48 weeks after therapy initiation.

Methods: One hundred and thirty-two adults and children with TRE receiving CBD were studied prospectively. Participants were separated into two groups - either taking (CBD + clobazam) or not taking concomitant clobazam (CBD - clobazam). In the secondary analyses, participants were divided into groups depending on whether they were taking at least 1/4 of the other AEDs shown to interact with CBD (iAED). Seizure counts and Chalfont Seizure Severity Scale (CSSS) were obtained at baseline, 12, 24, and 48 weeks. Groups were compared at each respective time point in the study using generalized estimating equations (GEE) analyses.

Results: All groups demonstrated statistically significant reductions in seizure frequency and severity from baseline (all P < 0.05). When participants on CBD + clobazam were compared with CBD - clobazam, there were no significant differences in seizure frequency and severity reduction between the groups at 12 weeks (both P > 0.05). When comparing groups with iAEDs vs. group without iAEDs, independent of coadministration of clobazam, no differences in treatment response were observed (all P > 0.05). Longitudinal analyses up to 48 weeks after therapy initiation did not reveal any differences in treatment response between groups.

Conclusion: These analyses suggest that concomitant to CBD, AEDs may not have an effect on reducing seizure frequency and severity in patients with TRE.
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http://dx.doi.org/10.1016/j.yebeh.2019.07.008DOI Listing
September 2019

Cognitive functioning following long-term cannabidiol use in adults with treatment-resistant epilepsy.

Epilepsy Behav 2019 08 18;97:105-110. Epub 2019 Jun 18.

University of Alabama at Birmingham, Department of Neurology, Birmingham, AL, USA.

Cognitive dysfunction is a common comorbidity in adults with treatment-resistant epilepsy (TRE). Recently, cannabidiol (CBD) has demonstrated efficacy in epilepsy treatment. However, our understanding of CBD's cognitive effects in epilepsy is limited. We examined long-term cognitive effects of CBD in adults with TRE as part of an ongoing prospective, open-label safety study. Twenty-sevenadults with TRE (mean age: 34[SD +14], female 52%) enrolled in the UAB CBD program completed standardized cognitive testing (NIH Toolbox Cognition Battery (NIHTB-CB)) at pre-CBD administration baseline and at one-yearfollow-up. Participants were receiving stable CBD dose at the time of one-year testing (mean=36.5mg/kg/day). The NIHTB-CB consisted of two global composite scales (Fluid and Crystallized) and seven individual tests measuring aspects of working memory, episodic memory, executive function, processing speed, and language. All participants had recorded Chalfont Seizure Severity Scale (CSSS) scores at each visit. Statistical analyses consisted of t-test, Pearson correlation coefficient, and linear regression. At baseline, cognitive test performance was below average for both global composite scales (Fluid: 71 [±18] range: 46-117) and Crystallized (76 [±15] range: 59-112)]. Longitudinal analysis revealed no significant group change across the two global composite scales. Of the seven individual cognitive tests, none changed significantly over time. No correlation was found between the cognitive change scores and CBD dose (all P's≥0.21). Change in cognitive test performance was not associated change in seizure severity rating. These findings are encouraging and indicate that long-term administration of pharmaceutical grade CBD is overall cognitively well-tolerated in adults with TRE.
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http://dx.doi.org/10.1016/j.yebeh.2019.04.044DOI Listing
August 2019

Higher cannabidiol plasma levels are associated with better seizure response following treatment with a pharmaceutical grade cannabidiol.

Epilepsy Behav 2019 06 29;95:131-136. Epub 2019 Apr 29.

Biostatistics, Birmingham, AL, USA.

Objective: The objective of this study was to determine the relationship between cannabidiol (CBD) dose, CBD plasma level, and seizure control in a large open-label single-center study.

Methods: All participants with treatment-refractory epilepsy participating in our expanded access program (EAP) were approached for participation. Highly purified grade CBD (Epidiolex®) dosing was weight-based and could be increased every 2 weeks by 5 mg/kg/day up to a maximum dosage of 50 mg/kg/day depending on tolerance and seizure control. Seizure counts were obtained at each visit with frequency calculated per 2-week periods. Cross-sectional plasma peak levels of CBD were obtained ~4 h after dosing in consecutively presenting patients.

Results: We evaluated 56 adults and 44 children (100 total; 54 female) at two time points - one before initiating CBD and one at the time of CBD plasma level testing. There was a positive linear correlation between CBD dosage (range from 5 to 50 mg/kg/day) and level (range from 7.1-1200 ng/mL) in all participants (r = 0.640; p < 0.001). The quantile regression model supported the notion of increased CBD levels being associated with improvement in seizure frequency after adjusting for age - specifically, a 100 ng/mL increase in CBD level was associated with approximately two counts reduction in seizure frequency per time period (1.87 96% confidence interval [CI] 0.34-3.39; p = 0.018). In participants with the same CBD level, differences in seizure improvement did not depend on age (p = 0.318).

Conclusions: In this open-label study, we found evidence of a linear correlation between CBD dosage and plasma levels, and that higher dose/levels are associated with a higher response rate for seizure improvement. Children and adults responded to CBD similarly. However, seizure control response rates suggest children may respond to lower dosages/plasma levels than adults. Findings reported in this study are specific to Epidiolex® and should not be extrapolated to other CBD products.
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http://dx.doi.org/10.1016/j.yebeh.2019.03.042DOI Listing
June 2019

Association between trace elements in the environment and stroke risk: The reasons for geographic and racial differences in stroke (REGARDS) study.

J Trace Elem Med Biol 2017 Jul 7;42:45-49. Epub 2017 Apr 7.

Department of Epidemiology & Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA. Electronic address:

The disparities in stroke mortality between blacks and whites, as well as the increased stroke mortality in the "stroke belt" have long been noted. The reasons for these disparities have yet to be fully explained. The association between trace element status and cardiovascular diseases, including stroke, has been suggested as a possible contributor to the disparities in stroke mortality but has not been fully explored. The purpose of this study is to investigate distributions of four trace elements (arsenic, mercury, magnesium, and selenium) in the environment in relation to stroke risk. The study population (N=27,770) is drawn from the Reasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort. Environmental distribution of each trace element was determined using data from the United States Geological Survey (USGS) and was categorized in quartiles. A proportional hazards model, adjusted for demographic data and stroke risk factors, was used to examine the association of interest. The results showed that higher selenium levels in the environment were associated with increased stroke risk, and the hazard ratio for the 4th quartile compared to the 1st quartile was 1.33 (95% CI: 1.09, 1.62). However, there was no statistically significant relationship between environmental arsenic, mercury or magnesium and the risk of stroke. Because of dietary and non-dietary exposure as well as bioavailability, further research using biomarkers is warranted to examine the association between these trace elements and the risk of stroke.
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http://dx.doi.org/10.1016/j.jtemb.2017.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481160PMC
July 2017

Fish oil supplementation ameliorates fructose-induced hypertriglyceridemia and insulin resistance in adult male rhesus macaques.

J Nutr 2014 Jan 9;144(1):5-11. Epub 2013 Oct 9.

Departments of Pediatrics, and.

Fish oil (FO) is a commonly used supplemental source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), 2 n-3 (ω-3) polyunsaturated fatty acids (PUFAs) that have been shown to have a variety of health benefits considered to be protective against cardiometabolic diseases. Although the effects of EPA and DHA on lipid metabolism have been extensively studied, not all of the metabolic effects of FO-derived n-3 PUFAs have been characterized. Our laboratory recently showed that a high-fructose diet in rhesus monkeys induces the features of metabolic syndrome (MetS) similar to those observed in humans. Thus, we specifically wanted to evaluate the effects of FO in rhesus monkeys fed a high-fructose diet and hypothesized that FO supplementation would mitigate the development of fructose-induced insulin resistance, dyslipidemia, and other cardiometabolic risk factors. In this study, adult monkeys (aged 12-20 y) received either a standard unpurified diet plus 75 g fructose/d (control group; n = 9) or a standard unpurified diet, 75 g fructose/d, and 4 g FO (16% EPA + 11% DHA)/d (treatment group; n = 10) for 6 mo. Importantly, our results showed that daily FO supplementation in the monkeys prevented fructose-induced hypertriglyceridemia and insulin resistance as assessed by intravenous-glucose-tolerance testing (P ≤ 0.05). Moreover, FO administration in the monkeys prevented fructose-induced increases in plasma apolipoprotein (Apo)C3, ApoE, and leptin concentrations and attenuated decreases in circulating adropin concentrations (P ≤ 0.05). No differences between the control and FO-treated monkeys were observed in body weight, lean mass, fat mass, or fasting glucose, insulin, and adiponectin concentrations. In conclusion, FO administration in a nonhuman primate model of diet-induced MetS ameliorates many of the adverse changes in lipid and glucose metabolism induced by chronic fructose consumption.
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http://dx.doi.org/10.3945/jn.113.178061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3861794PMC
January 2014

Developmental outcomes in early school-age children with minimal hearing loss.

Am J Audiol 2013 Dec;22(2):263-70

Purpose: Previous research suggests that school-age children with minimal hearing loss (CMHL) are at risk for a variety of psychoeducational problems. However, CMHL are a heterogeneous group, and the profile of at-risk children is unknown. Data regarding the characteristics of early school-age CMHL are needed to extend previous findings and determine potential risk factors associated with psychoeducational difficulties.

Method: Psychoeducational outcomes were evaluated at baseline and longitudinally in age-matched groups of 27 CMHL (ages 4–10 years) and 26 children with normal hearing (CNH) using assessments of language, reading, behavior, speech recognition in noise, and cognition. Additional analyses were used to identify demographic characteristics among CMHL that are associated with psychoeducational difficulties.

Results: At the earliest age tested, CMHL had greater teacher-rated attention difficulties in the classroom than CNH. Differences in the rate of psychoeducational development were not observed between groups. Among CMHL, psychoeducational difficulties were associated with delays in identification of hearing loss and low maternal education.

Conclusions: Classroom attention abilities should be monitored for early school-age CMHL. Late-identified CMHL and CMHL with low maternal education levels may be in particular need of academic and social support. Continued efforts for early identification of CMHL should be made to improve outcomes for these children.
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http://dx.doi.org/10.1044/1059-0889(2013/13-0013)DOI Listing
December 2013

Generic levothyroxine compared with synthroid in young children with congenital hypothyroidism.

J Clin Endocrinol Metab 2013 Feb 4;98(2):653-8. Epub 2013 Jan 4.

Department of Pediatrics, Division of Endocrinology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-9170, USA.

Context: Clinicians who prescribe levothyroxine (LT4) for hypothyroidism often feel strongly about using a brand-name drug instead of a generic.

Objective: The objective of the study was to determine whether Synthroid resulted in better control of congenital hypothyroidism than generic LT4.

Design: This was a 5-year retrospective study.

Setting: The study was conducted at 1 tertiary care center.

Patients: Children who were 0-36 months old with congenital hypothyroidism followed up at our center from 2006 to 2011 were treated with either Synthroid exclusively (35 subjects) or generic LT4 exclusively (27 subjects).

Interventions: We recorded the subjects' TSH and free T(4) measurements, how often their LT4 dose was adjusted, and the duration of follow-up.

Main Outcome Measure: TSH variance between the groups was measured. Secondary end points were the frequency of LT4 dose changes and the variance in free T(4).

Results: Using the Wilcoxon rank sum test, there was no difference in TSH SD in the Synthroid group compared with the generic group (median 3.0 vs 2.2, P = .27). Using a linear mixed model, children treated with the generic LT4 had lower TSH estimated SD [1.35 with 95% confidence interval (CI) (1.194, 1.526)] than the Synthroid group [1.66 with 95% CI (1.536, 1.803)]. Similarly, no difference was observed in free T(4) SD between the groups using the Wilcoxon rank sum test (median 0.29 generic vs 0.36 Synthroid, P = .11), but the generic group had lower free T(4) estimated SD than the Synthroid group using the linear mixed model [0.216 with 95% CI (0.187, 0.249) vs 0.298 with 95% CI (0.273,0.326)]. Frequency of LT4 dosing adjustments was similar between the groups, both in total (median 2.0 for generic vs 3.0 for Synthroid, P = .097) and when adjusted for number of TSH checks (ratio 0.25 generic vs 0.31 Synthroid, P = .45).

Conclusions: In our study of congenital hypothyroidism, generic LT4 treatment resulted in similar or better control of hypothyroidism compared with Synthroid, as assessed by the clinical outcomes of TSH variance and the frequency of LT4 dosing adjustments.
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http://dx.doi.org/10.1210/jc.2012-3558DOI Listing
February 2013