KETOGENIC DIET IN CHILDREN WITH MEDICALLY REFRACTORY SEIZURE

难治性癫痫儿童的生酮饮食

• 批准号: 6219817
• 负责人: LAWRENCE S BROWN
• 金额: $ 0.06万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219817
• 关键词: bioenergetics; body composition; bone density; child (0-11); clinical research; diet therapy; epilepsy; human subject; human therapy evaluation; ketone body; nutrition related tag

Between December 1st 1997 and November 30th 1998 there were no new subjects enrolled into this study. Four follow up studies were performed. The last follow up study was completed by March 1998, and data analysis is now (as of February 1999) complete. Based on this pilot study of the growth and nutrition of children with intractable epilepsy on the ketogenic diet we conclude the following. Preliminary Studies Aim 1: To determine the efficacy of the standard 4:1 ketogenic diet (KD) As part of a pilot study of the growth and nutritional status of children on the currently recommended 4:1 KD preceded by a fast, efficacy was measured. Twenty-five subjects with intractable epilepsy were enrolled over a two-year time interval and followed prospectively for 6 months. Follow-up evaluations were scheduled at 1, 3 and 6 months. We defined efficacy as >50%reduction of baseline seizure frequency. Change in seizure frequency was tabulated from the parent's daily seizure calendars and the average seizure frequency (number of seizures per week) occurring during 28 days before the 3-and 6-month follow-up visits were compared with baseline. The percentage decrease in seizures from baseline was used to assess the efficacy of the diet. Adverse events were also noted. Aim 2: To determine if the restrictive nature of the KD places the children at risk for nutritional deficiencies that will impair growth rate and accretion of fat-free mass. The second project was a longitudinal study of growth and nutritional status of children with intractable epilepsy treated with the KD. The same 25 subjects were followed at baseline, 1-month, 3-months and 6-months on the KD treatment. Weights and heights were obtained and measurements were converted to Z scores. Body composition was obtained using the dual energy x-ray absorptiometry (DXA) and expressed as fat-free mass (FFM) (lean mass + bone mass) and % body fat. Aim 3: To determine if children on the ketogenic diet are at risk for osteopenia. It is well known that anticonvulsants may predispose children to osteopenia through alterations in vitamin D and calcium metabolism. Whether the KD worsens this effect has not been well studied. We evaluated bone health in 14 of the 25 children by measuring Lumbar AP spine bone density (BMD) and bone mineral content (BMC) before the KD and at 3 months into the maintenance diet. Aim 4: To determine if change in substrate utilization as measured by the respiratory quotient (RQ) can predict who will respond to treatment with the ketogenic diet. The mechanism of the KD remains unknown. The currently recommended KD protocol at CHOP requires a 3 month commitment (because of some late responders) before efficacy can be determined. A predictor of response would simplify the management of these patients. We measured Resting Energy Expenditure (REE) and RQ in the previously described 25 subject to see if changes in substrate utilization as measure by the RQ could predict response to KD.

1997年12月1日至1998年11月30日期间，本研究未入组新受试者。 进行了4项随访研究。最后一次随访研究于1998年3月完成，数据分析现已完成（截至1999年2月）。 根据这项生酮饮食对难治性癫痫儿童生长和营养的初步研究，我们得出以下结论。初步研究目标1：为了确定标准4：1生酮饮食（KD）的疗效，作为目前推荐的4：1 KD之前快速的儿童生长和营养状况的试点研究的一部分，测量了疗效。 25例难治性癫痫受试者在2年的时间间隔内入组，并前瞻性随访6个月。 计划在1、3和6个月时进行随访评价。 我们将有效性定义为基线癫痫发作频率减少> 50%。 根据父母的每日癫痫发作日历对癫痫发作频率的变化进行制表，并将3个月和6个月随访访视前28天内发生的平均癫痫发作频率（每周癫痫发作次数）与基线进行比较。 使用癫痫发作较基线减少的百分比来评估饮食的有效性。 还记录了不良事件。目标二：确定KD的限制性性质是否会使儿童面临营养缺乏的风险，从而影响生长速度和无脂肪质量的增加。第二个项目是一项对KD治疗的难治性癫痫儿童的生长和营养状况的纵向研究。 在基线、KD治疗1个月、3个月和6个月时对相同的25名受试者进行随访。 获得体重和身高，并将测量值转换为Z评分。 使用双能X射线吸收测定法（DXA）获得身体组成，并表示为去脂质量（FFM）（瘦体重+骨量）和%体脂。目的3：确定生酮饮食的儿童是否有骨质减少的风险。众所周知，抗惊厥药可能通过改变维生素D和钙代谢而使儿童易患骨质减少症。 KD是否会影响这种效应还没有得到很好的研究。 我们通过测量KD前和维持饮食3个月时的腰椎AP脊柱骨密度（BMD）和骨矿物质含量（BMC）来评估25名儿童中14名儿童的骨健康状况。目标4：确定通过呼吸商（RQ）测量的底物利用率变化是否可以预测生酮饮食治疗的反应。KD的机制仍然未知。 CHOP目前推荐的KD方案需要3个月的承诺（因为一些晚期应答者）才能确定疗效。 反应的预测器将简化这些患者的管理。 我们测量了先前描述的受试者的静息能量消耗（REE）和RQ，以观察通过RQ测量的底物利用率的变化是否可以预测对KD的响应。