肝細胞生長因子顯示有益於糖尿病性疼痛


  【24drs.com】新研究認為,人類的肝細胞生長因子(HGF; VM202, ViroMed)注射劑,在2週期間內注射2次,可以顯著減少糖尿病周邊神經性疼痛達3個月之久,且無明顯副作用。
  
  共同作者、西北大學Feinberg醫學院神經科教授John Kessler醫師表示,我們發現,沒有服用pregabalin或gabapentin的病患對HGF的反應特別好,這一點特別重要,因為有些病患無法服用這些藥物或者對它們反應不佳,所以,我們希望可以為這些病患提供一些治療選項。
  
  Kessler醫師等作者解釋,已知HGF對於周邊感覺、交感神經、和運動神經元有營養作用,滋養神經元的存活和軸突生長。
  
  他們寫道,HGF的強大神經營養和血管生成的性質,讓它相當適合用來治療糖尿病神經病變疼痛。
  
  這篇發表於美國神經科協會(ANA)2015年會的雙盲研究,共有104名糖尿病神經病變疼痛患者被隨機分組,在兩腳的小腿肌肉各注射質體VM202 8 mg或16 mg或安慰劑,2次注射間隔2週。
  
  完成研究的96名患者中,低劑量組(n = 40人)在各種效果測量的改善幅度最大,3個月時的平均疼痛分數顯著降低(P = .04),測量工具是每日疼痛與睡眠干擾量表,將受試者的24小時平均疼痛與睡眠干擾量化。
  
  作者們報告指出,疼痛減少的效果在第6和第9個月時持續,但是未達統計上的顯著程度。
  
  低劑量組,沒有服用pregabalin或gabapentin的病患(n = 49人),每日疼痛與睡眠干擾量表分數的降低幅度最大,3個月時明顯降低3.7分(P = .02),他們的疼痛減輕效果維持到6個月(P = .03)以及9個月時(P = .08)。
  
  作者們推論指出,研究結果認為pregabalin或gabapentin與HGF之間有交互作用。
  
  他們寫道,因為在任何的人口統計學項目、HbA1c [糖化血色素A1c]值、患病期間、納入研究時的疼痛情況等皆未觀察到差異,這個研究發現可能代表的是,這些藥物的作用機轉不知何故減弱了HGF活性。
  
  在其他疼痛測量中,低劑量組的病患整體報告指出,病人整體改變印象(PGI)問卷結果,在90天、6個月、9個月時,低劑量組的改善最大。
  
  90天時,低劑量組48.4%的病患(31人中的15人)和高劑量組30.6%的病患(36人中的11人)報告指出,PGI分數有很多或非常多的改善,亦即疼痛減少幅度大於50%,而安慰劑組患者只有 17.6%(17人中的3人)達到。
  
  疼痛嚴重度的降低是根據糖尿病周邊神經病變簡明疼痛量表進行測量,相較於安慰劑組,低劑量組在第3個月和第6個月時有顯著改善(3個月時,–41.95% [P = .06],6個月時,–37.71% [P = .05]),而高劑量組的疼痛嚴重度分數改善程度未達統計上的顯著意義。
  
  重要的是,Kessler醫師瞭解HGF/VM202治療是一種非病毒基因治療,它不同於其他的基因治療。已知,基因治療與DNA上病毒表現的相關併發症有關。
  
  他表示,雖然這篇研究沒有比較其他藥物相關的疼痛改善療法,這些反應看起來都大於對其他藥物的預期。
  
  Kessler醫師表示,如果你探討疼痛反應文獻,我們的疼痛改善幅度大於其他藥物,所以,它看起來至少跟既有的療法一樣是有效的。
  
  他指出,病患在感覺輕微碰觸與機械式碰觸之功能也有改善。所以,藉由HGF治療,我們不只可改善疼痛,也可改善功能。
  
  研究期間, 10名患者發生13件嚴重副作用,但是都與研究藥物或安慰劑無關;26名患者發生等級1的輕微注射部位反應,超過半數是高劑量組患者。
  
  作者們寫道,HGF治療的一個顯著特點是,幾乎沒有副作用,這可能反映了一個事實,也就是這項治療是局部而不是全身性的。
  
  Kessler醫師指出,能減少疼痛且不用每天用藥的療法,對於有神經病變疼痛的糖尿病患是有顯著幫助的。
  
  他表示,我們探討的是一年兩個循環、進行4次治療的療法,而不用每天吃藥,這將會是很有幫助的。
  
  研究者將在2016年1月進行VM202的第三階段研究,將有477名病患以2比1的比率分組進行藥物與安慰劑的比較。
  
  這篇研究也發表於臨床與轉化神經學誌。
  
  資料來源:http://www.24drs.com/
  
  Native link:Hepatocyte Growth Factor Shows Benefit for Diabetic Pain

Hepatocyte Growth Factor Shows Benefit for Diabetic Pain

By Nancy A. Melville
Medscape Medical News

CHICAGO — Human hepatocyte growth factor (HGF; VM202, ViroMed) injections, administered twice over 2 weeks, show efficacy in significantly reducing diabetic peripheral neuropathic pain for up to 3 months without any significant adverse effects, new research suggests.

"We found that patients who were not taking pregabalin or gabapentin responded particularly well to HGF, and that's particularly important because some patients are unable to take these drugs or don't respond to them, so we would have something to offer those patients with this," co-author John Kessler, MD, a professor of neurology at Northwestern University’s Feinberg School of Medicine, told Medscape Medical News.

HGF is known to have trophic effects on peripheral sensory, sympathetic, and motor neurons, nourishing neuronal survival and axonal growth, Dr Kessler and the authors explain.

"HGF's potent neurotrophic and angiogenic properties make it the ideal candidate for the treatment of painful diabetic neuropathy," they write.

For the double-blind study, presented here at the American Neurological Association (ANA) 2015 Annual Meeting, 104 patients with painful diabetic neuropathy were randomly assigned to receive intramuscular injections in the calves, with 8 mg of the plasmid VM202 per leg, 16 mg per leg, or placebo. The injections were administered 2 weeks apart.

Among 96 patients who completed the study, those in the low-dose group (n = 40) reported the greatest improvement in all measures of efficacy and a significant reduction in mean pain score at 3 months (P = .04), as determined by scores on the Daily Pain and Sleep Interference Diary, which quantified participants' average 24-hour pain and sleep interference.

The authors reported that pain reductions persisted at 6 and 9 months but were not statistically significant.

Patients in the low-dose group who were not taking pregabalin or gabapentin (n = 49) reported the largest reductions in pain in terms of scores on the Daily Pain and Sleep Interference Diary, showing a significant 3.7-point reduction in pain at 3 months (P = .02). Their pain reduction was maintained at 6 months (P =.03) and 9months (P=.08).

The authors speculated that the findings suggest an interaction between pregabalin or gabapentin and HGF.

"As there were no observable differences between these patient populations for any demographic, HbA1c [hemoglobin A1c] levels, duration of disease, or pain at study entry, this finding may suggest that the mechanism of action of these drugs somehow attenuates HGF activity," they write.

In terms of other pain measures, patients in the low-dose group overall also reported the greatest degree of improvement on the Patient’s Global Impression (PGI) of Change questionnaire at 90-day and 6- and 9-month visits.

At 90days, 48.4% (15 of 31) of patients in the low-dose group and 30.6% (11 of 36) of patients in the high-dose group reported being much or very much improved on the PGI scale, with a reduction in pain greater than 50%, compared with only 17.6% (3 of 17) of patients in the placebo group.

Reductions in pain severity, determined by using the Brief Pain Inventory for Diabetic Peripheral Neuropathy, were significant in the low-dose group at 3 and 6 months compared with placebo (–41.95% at 3 months [P =.06] and –37.71% at 6 months [P =.05]), while improvements in the pain severity score in the high-does group did not reach statistical significance.

Dr Kessler underscored that HGF/VM202 therapy is, importantly, a nonviral gene therapy, as opposed to other gene therapies that have been associated with complications linked to viruses expressed in the DNA.

While the study did not compare the therapy with pain improvement related to other drugs, the response appears greater than that typically expected with other medications, he said.

"If you look at the literature on pain response, we had a much greater reduction in pain than other medications, so it looks like it's at least as effective, if not more, than existing therapies," Dr Kessler said.

Patients also showed improvement in functions such as ability to sense light touch and mechanical touch, he added.

"So we may not just be improving pain but also function with the HGF therapy."

During the study 13 serious adverse events occurred among 10 patients, but none were considered to be related to the study drug or placebo.

Twenty-six patients experienced grade 1 minor injection site reactions, with more than half in the high-dose group.

"One of the striking features of the HGF treatment is that there were virtually no side effects, which probably reflects the fact that the treatment was local rather than systemic," the authors write.

Dr Kessler added that the ability to have pain reduction without the need for daily medication could be a significant benefit to diabetic patients with neuropathic pain.

"We're looking at treating patients in two cycles four times a year as opposed to taking a medicine every day — that would be very helpful," he said.

The researchers are moving ahead with a phase 3 study on VM202 that is scheduled to begin in January 2016, with approximately 477 patients to be evaluated in a 2:1 ratio of drug vs placebo.

The study was also published in the Annals of Clinical and Translational Neurology.

The study’s costs were paid for by ViroMed. Dr Kessler has disclosed no relevant financial relationships.

American Neurological Association (ANA) 2015 Annual Meeting. Abstract M703. Presented September 28, 2015.

    
相關報導
單靠篩檢與治療無法預防第二型糖尿病
2017/1/12 上午 11:07:07
別老是坐著 少坐一點對糖尿病有好處
2016/12/9 上午 10:05:25
Metformin失敗之後 延遲強化治療常見
2016/8/31 下午 01:57:15

上一頁
   1   2   3   4   5   6   7   8   9   10  




回上一頁