Get access

Propentofylline for dementia

  • Review
  • Intervention

Authors


Abstract

Background

Propentofylline is a novel therapeutic agent for dementia that readily crosses the blood-brain barrier and acts by blocking the uptake of adenosine and inhibiting the enzyme phosphodiesterase. In vitro and in vivo its mechanism of action appears to be twofold; it inhibits the production of free radicals and reduces the activation of microglial cells. It therefore interacts with the inflammatory processes that are thought to contribute to dementia, and given its mechanism of action is a possible disease modifying agent rather than a purely symptomatic treatment.

Objectives

To determine the clinical efficacy and safety of propentofylline for people with dementia.

Search methods

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 10 January 2008 using the terms: propentofylline OR hextol OR karsivan. The CDCIG Specialized Register contains records from all major health care databases (CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources.

Aventis, the manufacturing pharmaceutical company, was asked for data from unpublished studies but declined to enter into correspondence.

Selection criteria

Unconfounded double-blind randomized controlled trials of propentofylline compared with a placebo or another treatment group.

Data collection and analysis

There were detailed reports of only four of the nine included studies. The efficacy of propentofylline was reviewed for undifferentiated dementia as there were not enough data to attempt a subgroup analysis for the types of dementia.

Main results

The following statistically significant treatment effects in favour of propentofylline are reported.
Cognition at 3, 6 and 12 months including MMSE at 12 months. [MD 1.2, 95%CI 0.12 to 2.28, P=0.03]
Severity of dementia at 3, 6 and 12 months including CGI at 12 months [MD -0.21, 95%CI -0.39 to -0.03, P=0.03].
Activities of Daily Living (NAB) at 6 and 12 months [MD -1.20, 95%CI -2.22 to -0.18, P=0.02].
Global Assessment (CGI) at 3 months [MD -0.48, 95% CI -0.75 to -0.21, P=0.0006], but not at later times.
Tolerability
There were minimal data on adverse effects and drop-outs. There were a statistically significant treatment effects in favour of placebo at 12 months, for the number of dropouts [OR=1.43, 95%CI 1.04 to 1.90, P=0.03].

Authors' conclusions

There is limited evidence that propentofylline might benefit cognition, global function and activities of daily living of people with Alzheimer's disease and/or vascular dementia. The meta-analyses reported here are far from satisfactory as a summary of the efficacy of propentofylline, considering the unpublished information on another 1200 patients in randomized trials that exists. Unfortunately Aventis has been unwilling to correspond with the authors, significantly limiting the scope of this review.

摘要

背景

Propentofylline用於癡呆症

Propentofylline是一種治療癡呆症的新型藥物,可以穿透血腦障壁(bloodbrain barrier),並藉由阻礙adenosine的攝取及限制phosphodiesterase酵素而發揮作用。 Propentofylline在體外與體內有兩種機制;它可以限制自由基產生,並且降低微神經交細胞的活性。 因此它可以與發炎反應交互作用(發炎被認為是癡呆症成因之一),並且假設它的作用機制可以改善疾病而非僅是處置症狀。

目標

確定對於癡呆症患者施予propentofylline的臨床療效及安全性。

搜尋策略

透過最近一次更新搜尋Specialized Register of the Cochrane Dementia and Cognitive Improvement Group以找出試驗,時間是2005年8月5日。 此外並向Aventis要求未發表的研究數據,不過對方拒絕回應。

選擇標準

以propentofylline與安慰劑或是其他治療進行比較的未受干擾的隨機對照試驗。

資料收集與分析

被納入的9個研究中只有4個具備詳細的報告。由於相關數據不夠充足,因此在回顧propentofylline的療效的時候不進行子群組分析,而是以不區分癡呆症種類進行分析。

主要結論

報告顯示有統計上顯著療效贊成使用propentofylline。 ■於3、6、12個月的認知狀態及第12個月MMSE(簡式智能量表)的資料[MD 1.2, 95%CI 0.122.28, P = 0.03]。 ■在3、6、12個月癡呆症的嚴重程度以及第12個月時的CGI(臨床整體印象 −嚴重度)[MD −0.21, 95%CI −0.39 ∼ −0.03, P = 0.03]。 ■在6月及12月時[MD −1.20, 95%CI −2.22∼0.18, P = 0.02]。在3個月時CGI為[MD −0.48, 95% CI −0.75∼0.21, P = 0.0006]但此數值不在之後的月份出現。 ■耐受度 關於不良反應與退出試驗的數據很少。不過在退出試驗人數方面,統計上顯著較為偏好安慰劑[OR = 1.43, 95%CI 1.04∼1.90, P = 0.03]。

作者結論

有限的證據證實propentofylline可能對於阿茲海默症及/或血管型癡呆症患者的日常生活活動之認知、整體功能及日常生活活動有幫助。 由於未發表的隨機試驗當中尚有1200位病人的數據,因此統合分析(metaanalyses)在此所報告的propentofylline療效概述難以令人滿意。此外,很不幸的Aventis不願意與本回顧的作者連繫,大幅限制了本回顧的應用。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

有限的證據證實propentofylline可能對於阿茲海默症及/或血管型癡呆症患者的日常生活活動之認知、整體功能及日常生活活動有幫助。 Propentofylline是一種公認的新型神經保護藥物,藉著阻止adenosine的攝取及阻礙phosphodiesterase酵素而發揮作用。 雖然已經進行了一些隨機對照的試驗,不過僅能從數量有限的研究中獲得數據。有限的資料顯示propentofylline對於患有阿茲海默疾病或血管性癡呆症人們的認知及整體功能可能有良好的療效。 由於藥廠Aventis公司拒絕提供未發表的研究數據,因此無法取得相關數據,造成無法進行全面系統性文獻回顧以及統合分析。

Plain language summary

Limited evidence that propentofylline benefits cognition, global function and activities of daily living in people with Alzheimer's disease and/or vascular dementia

Propentofylline is a novel putatively neuroprotective agent that acts by inhibiting the uptake of adenosine and blocking the enzyme phosphodiesterase. Although a number of randomized controlled trials have been undertaken, data were available from only a very limited number of these studies. These limited data suggest that propentofylline may have a beneficial effect on measures of cognitive and global function of people with Alzheimer's or vascular dementia. The unavailability of data, due to failure of Aventis, the manufacturing pharmaceutical company, to release information about unpublished studies prevented a comprehensive systematic review and meta-analysis.

Get access to the full text of this article

Ancillary