Evaluating the safety, tolerability, pharmacokinetics and efficacy of clofazimine in cryptosporidiosis (CRYPTOFAZ): study protocol for a randomized controlled trial.
Evaluating the safety, tolerability, pharmacokinetics and efficacy of clofazimine in cryptosporidiosis (CRYPTOFAZ): study protocol for a randomized controlled trial.
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DOI：
10.1186/s13063-018-2846-6
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发表时间：
2018-08-23
期刊：
影响因子：
2.5
通讯作者：
Iroh Tam PY
中科院分区：
文献类型：
--
作者：
Nachipo P;Hermann D;Quinnan G;Gordon MA;Van Voorhis WC;Iroh Tam PY
隐孢子虫感染和腹泻（隐孢子虫病）是艾滋病毒感染者以及发展中国家6-18个月儿童的致命感染。到目前为止，只有硝唑尼特被许可用于治疗隐孢子虫病，并且仅适用于一岁后和免疫系统健康的人。氯法齐明（CFZ：Lamprene®）是一种已被用于麻风病超过50年的成熟药物，最近被描述为在体外和小鼠感染中有效对抗隐孢子虫。尚不清楚CFZ在HIV感染伴隐孢子虫性腹泻患者体内的疗效和药代动力学。CFPTOFAZ包括一项随机、双盲、安慰剂对照研究，在HIV感染和慢性隐孢子虫腹泻受试者中评价CFZ口服给药的安全性、耐受性和隐孢子虫抑制活性。该研究的另一个开放标签方面将比较口服CFZ在有和无隐孢子虫相关腹泻的HIV感染个体中的药代动力学（PK）。本研究共招募66例受试者。研究受试者将在住院期间接受CFZ或安慰剂治疗5天，并在出院后接受随访。将通过定量PCR作为确定性试验和粪便ELISA诊断隐孢子虫，粪便ELISA也将用于定量粪便中隐孢子虫的脱落。将对血浆和粪便样本进行PK研究。主要终点包括5天内粪便中脱落的隐孢子虫数量的减少，与安慰剂接受者相比，以及通过曲线下面积、血浆峰浓度和末次给药后测定的半衰期（T1/2）评估的血浆中CFZ的PK。这项研究提供了一个机会，探索一种可能的治疗方案，为艾滋病毒感染的患者隐孢子虫腹泻，谁，截至目前在马拉维和撒哈拉以南非洲大部分地区，没有一个明确的治疗除了支持性护理。这项研究的优势在于它是一项随机、双盲、安慰剂对照试验。如果被证明是有效和安全的，研究结果也将为未来在6-18个月的儿童中使用CFZ的研究奠定基础。ClinicalTrials.gov，NCT 03341767。于2017年11月14日注册。本文的在线版本（10.1186/s13063-018-2846-6）包含补充材料，可供授权用户使用。
Cryptosporidium infection and diarrhea (cryptosporidiosis) is a life-threatening infection in persons with HIV and also in children of 6–18 months of age in the developing world. To date, only nitazoxanide is licensed for treatment of cryptosporidiosis, and only in persons after the first year of life and with healthy immune systems. Clofazimine (CFZ: Lamprene®), an established drug that has been used for leprosy for more than 50 years, recently has been described as effective against Cryptosporidium in vitro and in mouse infections. The efficacy and pharmacokinetics of CFZ in vivo, in HIV-infected patients with cryptosporidial diarrhea are not known. CRYPTOFAZ includes a randomized, double-blind, placebo-controlled study of the safety, tolerability and Cryptosporidium inhibitory activity of orally administered CFZ in subjects with HIV infection and chronic diarrhea with Cryptosporidium. An additional open label aspect of the study will compare the pharmacokinetics (PK) of orally administered CFZ in HIV-infected individuals with and without Cryptosporidium-associated diarrhea. The study will recruit a total of 66 subjects. Study participants will be given either CFZ or a placebo for 5 days while in hospital and will be followed up after discharge. Cryptosporidium will be diagnosed by quantitative PCR as the definitive test and by stool ELISA, which will also be used to quantify the shedding of Cryptosporidium in stool. PK will be studied on plasma and stool samples. Primary endpoints include reduction in the number of Cryptosporidium shed in stools over a 5-day period and compared to placebo recipients and the PK of CFZ in plasma assessed by area under the curve, peak plasma concentration, and half-life (T ½) determined after the last dose. This study provides an opportunity to explore a possible treatment option for HIV-infected patients with cryptosporidial diarrhea, who, as of now in Malawi and most of sub-Saharan Africa, do not have a definitive treatment apart from supportive care. The strength of this study lies in it being a randomized, double-blind, placebo-controlled trial. If shown to be effective and safe, the findings will also lay a foundation for a future study of the use of CFZ in children 6–18 months of age. ClinicalTrials.gov, NCT03341767. Registered on 14 November 2017. The online version of this article (10.1186/s13063-018-2846-6) contains supplementary material, which is available to authorized users.
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撒哈拉以南非洲和南亚的中等/高死亡率地区儿童中隐孢子虫腹泻病的负担，利用来自全球企业多中心研究（GEMS）的数据。
影响因子：
3.8
作者：
Sow SO;Muhsen K;Nasrin D;Blackwelder WC;Wu Y;Farag TH;Panchalingam S;Sur D;Zaidi AK;Faruque AS;Saha D;Adegbola R;Alonso PL;Breiman RF;Bassat Q;Tamboura B;Sanogo D;Onwuchekwa U;Manna B;Ramamurthy T;Kanungo S;Ahmed S;Qureshi S;Quadri F;Hossain A;Das SK;Antonio M;Hossain MJ;Mandomando I;Nhampossa T;Acácio S;Omore R;Oundo JO;Ochieng JB;Mintz ED;O'Reilly CE;Berkeley LY;Livio S;Tennant SM;Sommerfelt H;Nataro JP;Ziv-Baran T;Robins-Browne RM;Mishcherkin V;Zhang J;Liu J;Houpt ER;Kotloff KL;Levine MM
通讯作者：
Levine MM
影响因子：
4.9
作者：
Swanson, Rosemary V.;Adamson, John;Almeida, Deepak V.
通讯作者：
Almeida, Deepak V.
影响因子：
56.3
作者：
Checkley, William;White, A. Clinton, Jr.;Jaganath, Devon;Arrowood, Michael J.;Chalmers, Rachel M.;Chen, Xian-Ming;Fayer, Ronald;Griffiths, Jeffrey K.;Guerrant, Richard L.;Hedstrom, Lizbeth;Huston, Christopher D.;Kotloff, Karen L.;Kang, Gagandeep;Mead, Jan R.;Miller, Mark;Petri, William A., Jr.;Priest, Jeffrey W.;Roos, David S.;Striepen, Boris;Thompson, R. C. Andrew;Ward, Honorine D.;Van Voorhis, Wesley A.;Xiao, Lihua;Zhu, Guan;Houpt, Eric R.
通讯作者：
Houpt, Eric R.
影响因子：
4.9
作者：
VANRENSBURG, CEJ;JOONE, GK;ANDERSON, R
通讯作者：
ANDERSON, R
影响因子：
168.9
作者：
Amadi, B;Mwiya, M;Kelly, P
通讯作者：
Kelly, P