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The efficacy of sodium benzoate as an adjunctive treatment in early psychosis - CADENCE-BZ: study protocol for a randomized controlled trial

trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-1908-5

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The study by Lane et al. was based on 52 patients with chronic schizophrenia [12]. They reported a Cohen¡¦s effect size (d) of 1.53. Our patients (with early psychosis) tend to have slightly lower mean PANSS total scores (65.0), with a standard deviation of 14.3 units and it is anticipated that the effect size will be smaller in this group.

With an alpha value of 0.05, and power of 0.8,

we wish to be able to confidently detect a difference in mean PANSS total score of at least 7 units.

This will require 66 participants per group (n = 132). Over a 12-week period we predict an attrition rate of 15%. Thus, we will need to randomize approximately 160 subjects.

P values will be based on two-tailed tests with significance levels of 0.05.

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Protocol update and statistical analysis plan for CADENCE-BZ: a randomized clinical trial to assess the efficacy of sodium benzoate as an adjunctive treatment in early psychosis

trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3232-8

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The last participant was recruited in August 2018 with the final follow-up visit anticipated to be completed in October 2018.

The final participants are currently completing the study and the results will be published in the near future.

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Our sample size was reduced from 160 to 100 after we adjusted our SAP. We recalculated our sample size by revising our assumptions regarding the correlations for a variety of covariance structures and the number of repeated measures.

Using a two-tailed test with alpha set at 0.05 and 90% power, to detect a minimum clinical meaningful difference in total PANSS score of at least 5 units (SD = 14.3) between both treatment arms, we determined that we needed a sample of 39 persons in each group.

This assumes the correlation between baseline and follow-up measurements is at least 0.6 and the correlation between various follow-up measurements is at most 0.5. Over a 12-week period, we predicted an attrition rate of 20%.

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Coping with Illness Experiences in Patients with Schizophrenia: The Role of Peacefulness

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Peacefulness has an emotional component and a cognitive component. The participants described peacefulness as a carefree state of mind that consisted of an inner sense of tranquility (the emotional component) and perceived freedom (the cognitive component). Their illness experiences were a vicious circle that was formed and maintained by distress (negative emotions) and preoccupation (distorted cognition). They believed that an inner sense of tranquility (the emotional component) facilitated the regulation of their distress, leaving them more cognitive resources to stabilize their chaotic minds, whereas perceived freedom (cognitive component) created an intra psychic moment and space with no stress to free the patients from their preoccupation.

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¸É¥R¤@¤U

¨Æ¹ê¤W , p­È·|¤£·|¤p©ó 0.05 , ÃöÁä¦b©ót­È·|¤£·|¤j©ó 1.96

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®e¤pªº¦AÂû±C¤@¤U

½Ð¬Ý³o¨â²Õªº¤ñ¸û

(2) BRX90--placebo ²Õªº¤ñ¸û

1.BRX90 (n=45), placebo (n=46) ©Ò¥H¦Û¥Ñ«×¬O 45+46-2=89 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −3¡P7 [95% CI −6¡P9 to −0¡P5] ­pºâ SE

==> -6.9 = -3.7-1.96*SE

==> SE = 1.63265

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-3.7)/SE = 2.26625

4. ¥Î EXCEL ºâ±oªº p = 0.02586 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0252

study 2 :

BRX90--placebo ²Õªº¤ñ¸û

1.BRX90 (n=54), placebo (n=54) ©Ò¥H¦Û¥Ñ«×¬O 54+54-2=106 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −2¡P5 [95% CI −4¡P5 to −0¡P5] ­pºâ SE

==> -4.5 = -2.5-1.96*SE

==> SE = 1.020408

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-2.5)/SE = 2.45

4. ¥Î EXCEL ºâ±oªº p = 0.015923 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0160

¥ý½Ð¤j®a¬Ý¤@¤U³o¥÷¸ê®Æªº1, 2 ­¶---»¡©ú SD , SE , CI

ir.tari.gov.tw:8080/bitstream/345210000/240/1/78-7.pdf

³o¨â²Õ¤ñ¸û¼Æ¾Ú , ³Ì¥O¤HÅå³Yªº¬O , §Y¨Ï«Ü¤pªº¥­§¡­È®t²§ (¤@²Õ -3.7 , ¤@²Õ -2.5 )¤]·| p­È ¤p©ó0.05 , ¹F©óÅãµÛ

«á­±¤@²Õªº¥­§¡­È®t²§Áö¤ñ«e­±¤@²Õªº¤p , ¦ý¦]SE¤ñ¸û¤p , ³y¦¨ p ­È§ó¤p

¥­§¡­È®t²§¥u¦³ 2.5 ´N¥i¹F©óÅãµÛ , ¥H«eÁö¤]¦³°µ¦p¦¹¤p®t¶Zªº¼ÒÀÀ , ¦ý©È¦Û¤vºâ±oªº¦³»~ , ¤£´±¬Û«H

¤µ¬JµM¦³SAGEªºIII´Á¼Æ¾Ú§@¦õÃÒ , Åý¤H»´ÃP¤£¤Ö

³o¤]Ãø©Ç½²±Ð±Â¥s§Ú­Ì´Á¤¤¤ÀªR§O¤Ó°ª¿³ , «¢«¢?

¦Û§Ú³³¾K¤å , ¤wÄݾK¨¥¾K»y , ÁÙ¦³²¦³º§Ú­Ì¹ïSND-13ªº¼Æ¾Ú¤@µL©Òª¾ , ¤Á¤Å§@¬°§ë¸ê¨Ì¾Ú

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­Ü«P¤§¶¡ ¥²µM¦³¿ù ¤W«h¶K¤å ­×¥¿¦p¤U

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¨Ó·½¡GÂåÃÄÅ]¤è ¡@2019-03-21

med.sina.com/article_detail_103_2_63022.html

³ø¾É»¡¤F---¦b³Ì·sµoªí¦b¡m¬h¸­¤M¡n¤Wªº¢»´ÁÁ{§É¬ã¨sµ²ªGÅã¥Ü...

³Ì±`¨£ªºbrexanoloneªvÀø¬ÛÃö¤£¨}¨Æ¥ó¬°ÀYµh¡BÀY©ü¡B¶ÝºÎ¡Aµo¥Í4¨ÒªvÀø¬ÛÃöªºÄY­«¤£¨}¨Æ¥ó¡A¥]¬AÀH³X´Á¶¡¦Û±þ·N©À¡B¬G·NÃĪ«¹L¶q¡B·NÃѪ¬ºA§ïÅÜ»P·w³Ö¡C

brexanoloneªvÀø¬ÛÃö¤£¨}¨Æ¥ó¡A¤]¦³ÀH³X´Á¶¡¦Û±þ·N©À...

©ó¬O ¤pªº´N§ä¤F¡m¬h¸­¤M¡n( THE LANCET )ªº¬ÛÃö¢»´ÁÁ{§É¬ã¨sµ²ªGªº¼Æ¾Ú¸ê®Æ

www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31551-4/fulltext

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«¢! ¨Ó´ú¤@´ú¤pªº¤§«e¼ÒÀÀªº­pºâ , ¬O§_©MSAGE¢»´ÁÁ{§É¥Îªº­pºâµ²ªG¬Û¥h¬Æ»· ? ­Y¬Û¥h¬Æ»· , «h¼ÒÀÀ´Nµ¥©ó¬O¤@°ï©U§£°Õ!

¤pªº§â¡m¬h¸­¤M¡nªº¬ÛÃö¼Æ¾Ú ºK­n¦p¤U:

Findings :

We screened 375 women simultaneously across both studies, of whom 138 were randomly assigned to receive either BRX90 (n=45), BRX60 (n=47), or placebo (n=46) in study 1,

and 108 were randomly assigned to receive BRX90 (n=54) or placebo (n=54) in study 2.

In study 1, at 60 h, the least-squares (LS) mean reduction in HAM-D total score from baseline was 19¡P5 points (SE 1¡P2) in the BRX60 group and 17¡P7 points (1¡P2) in the BRX90 group compared with 14¡P0 points (1¡P1) in the placebo group (difference −5¡P5 [95% CI −8¡P8 to −2¡P2], p=0¡P0013 for the BRX60 group; −3¡P7 [95% CI −6¡P9 to −0¡P5], p=0¡P0252 for the BRX90 group).

In study 2, at 60 h, the LS mean reduction in HAM-D total score from baseline was 14¡P6 points (SE 0¡P8) in the BRX90 group compared with 12¡P1 points (SE 0¡P8) for the placebo group (difference −2¡P5 [95% CI −4¡P5 to −0¡P5], p=0¡P0160).

study 1 :

(1) BRX60--placebo ²Õªº¤ñ¸û

1.BRX60 (n=47), placebo (n=46) ©Ò¥H¦Û¥Ñ«×¬O 47+46-2=91 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −5¡P5 [95% CI −8¡P8 to −2¡P2] ­pºâ SE

==> -8.8 = -5.5-1.96*SE

==> SE = 1.68367

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-5.5)/SE = 3.266667

4. ¥Î EXCEL ºâ±oªº p = 0.001535 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0013

(2) BRX90--placebo ²Õªº¤ñ¸û

1.BRX90 (n=45), placebo (n=46) ©Ò¥H¦Û¥Ñ«×¬O 45+46-2=89 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −3¡P7 [95% CI −6¡P9 to −0¡P5] ­pºâ SE

==> -6.9 = -3.7-1.96*SE

==> SE = 1.63265

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-3.7)/SE = 2.26625

4. ¥Î EXCEL ºâ±oªº p = 0.02586 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0252

study 2 :

BRX90--placebo ²Õªº¤ñ¸û

1.BRX90 (n=54), placebo (n=54) ©Ò¥H¦Û¥Ñ«×¬O 54+54-2=106 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −2¡P5 [95% CI −4¡P5 to −0¡P5] ­pºâ SE

==> -4.5 = -2.5-1.96*SE

==> SE = 1.020408

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-2.5)/SE = 2.45

4. ¥Î EXCEL ºâ±oªº p = 0.015923 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0160

¥Ñ¤W­±¤T²Õ¼Æ¾Úªº¤ñ¸ûµû¦ô

¥Î EXCEL ºâ±oªº p ( Âù§À ) ©M SAGE³ø§i¦C¥Xªº p , ÁÙº¡¬Ûªñªº , ³o­Óµ²ªG©ÎÅý¤pªº¹ï¼ÒÀÀ§ó¼W²K¤@¨Ç«H¤ß

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FDA§å­ã­º­Ó²£«á§íÆ{·sÃÄ

¨Ó·½¡GÂåÃÄÅ]¤è ¡@2019-03-21

med.sina.com/article_detail_103_2_63022.html

³ø¾É»¡¤F---¦b³Ì·sµoªí¦b¡m¬h¸­¤M¡n¤Wªº¢»´ÁÁ{§É¬ã¨sµ²ªGÅã¥Ü...

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brexanoloneªvÀø¬ÛÃö¤£¨}¨Æ¥ó¡A¤]¦³ÀH³X´Á¶¡¦Û±þ·N©À...

©ó¬O ¤pªº´N§ä¤F¡m¬h¸­¤M¡n( THE LANCET )ªº¬ÛÃö¢»´ÁÁ{§É¬ã¨sµ²ªGªº¼Æ¾Ú¸ê®Æ

www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31551-4/fulltext

°µ¬Æ»ò¥Î©O ?

«¢! ¨Ó´ú¤@´ú¤pªº¤§«e¼ÒÀÀªº­pºâ , ¬O§_©MSAGE¢»´ÁÁ{§É¥Îªº­pºâµ²ªG¬Û¥h¬Æ»· ? ­Y¬Û¥h¬Æ»· , «h¼ÒÀÀ´Nµ¥©ó¬O¤@°ï©U§£°Õ!

¤pªº§â¡m¬h¸­¤M¡nªº¬ÛÃö¼Æ¾Ú ºK­n¦p¤U:

Findings :

We screened 375 women simultaneously across both studies, of whom 138 were randomly assigned to receive either BRX90 (n=45), BRX60 (n=47), or placebo (n=46) in study 1,

and 108 were randomly assigned to receive BRX90 (n=54) or placebo (n=54) in study 2.

In study 1, at 60 h, the least-squares (LS) mean reduction in HAM-D total score from baseline was 19¡P5 points (SE 1¡P2) in the BRX60 group and 17¡P7 points (1¡P2) in the BRX90 group compared with 14¡P0 points (1¡P1) in the placebo group (difference −5¡P5 [95% CI −8¡P8 to −2¡P2], p=0¡P0013 for the BRX60 group; −3¡P7 [95% CI −6¡P9 to −0¡P5], p=0¡P0252 for the BRX90 group).

In study 2, at 60 h, the LS mean reduction in HAM-D total score from baseline was 14¡P6 points (SE 0¡P8) in the BRX90 group compared with 12¡P1 points (SE 0¡P8) for the placebo group (difference −2¡P5 [95% CI −4¡P5 to −0¡P5], p=0¡P0160).

study 1 :

(1) BRX60--placebo ²Õªº¤ñ¸û

1.BRX60 (n=47), placebo (n=46) ©Ò¥H¦Û¥Ñ«×¬O 47+46-2=91 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −5¡P5 [95% CI −8¡P8 to −2¡P2] ­pºâ SE

==> -8.8 = -5.5-1.96*SE

==> SE = 1.68367

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-5.5)/SE = 3.266667

4. ¥Î EXCEL ºâ±oªº p = 0.001535 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0013

(2) BRX90--placebo ²Õªº¤ñ¸û

1.BRX90 (n=45), placebo (n=46) ©Ò¥H¦Û¥Ñ«×¬O 45+46-2=89 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −3¡P7 [95% CI −6¡P9 to −0¡P5] ­pºâ SE

==> -6.9 = -3.7-1.96*SE

==> SE = 1.63265

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-5.5)/SE = 2.26625

4. ¥Î EXCEL ºâ±oªº p = 0.02586 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0252

study 2 :

BRX90--placebo ²Õªº¤ñ¸û

1.BRX90 (n=54), placebo (n=54) ©Ò¥H¦Û¥Ñ«×¬O 54+54-2=106 (¥Î©ó­pºâ p ­È)

2.¥Î«H¿à°Ï¶¡(difference −2¡P5 [95% CI −4¡P5 to −0¡P5] ­pºâ SE

==> -4.5 = -2.5-1.96*SE

==> SE = 1.020408

3. ­pºâÀË©w²Î­p­È t = µ´¹ï­È(-5.5)/SE = 2.45

4. ¥Î EXCEL ºâ±oªº p = 0.015923 ( Âù§À )

5. SAGE³ø§i¦C¥Xªº p = 0¡P0160

¥Ñ¤W­±¤T²Õ¼Æ¾Úªº¤ñ¸ûµû¦ô

¥Î EXCEL ºâ±oªº p ( Âù§À ) ©M SAGE³ø§i¦C¥Xªº p , ÁÙº¡¬Ûªñªº , ³o­Óµ²ªG©ÎÅý¤pªº¹ï¼ÒÀÀ§ó¼W²K¤@¨Ç«H¤ß

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n = 24

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Add-on Treatment of Benzoate for Schizophrenia A Randomized, Double-blind, Placebo-Controlled Trial of D-Amino Acid Oxidase Inhibitor

greenlab.npih.ucla.edu/Publications/Lane%20et%20al.%20JAMA%20-%20Psychiatry%202013.pdf

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¬ü°ê UNC ¾ÇªÌ Rachel K. Silverman & Anastasia Ivanova ªº

Sample size re-estimation and other midcourse adjustments with sequential parallel comparison design

doi.org/10.1080/10543406.2017.1289951

P.4 ¦³¤@¬q¸Ü

In all of the adaptive strategies, we considered stopping for futility and efficacy. We stopped for

futility at the interim when Z1 < 0. To stop for efficacy, we used the O¡¦Brien-Fleming boundary with an interim look performed after the first half of the trial and stopped after Period 1 if Z1 > 2.7959.The final efficacy was established when Z > 1.977 (Fleming et al., 1984).(³o©M¤pªº¤W¦¸§@¼oªº¥H¥d¤è¤À°t¦ô¼Ë¥»¼Æªº¼ÒÀÀ , »á¦³²§¦±¦P¤u¤§§®)

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(2)

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¼Ð·Ç±`ºA¤À°tªºÀË©w­È Z = ( £g1-£g2 ) / (£m1^2/n1 + £m2^2/n2)^0.5 > 2.7959

©Ò¥H ( £g1-£g2 ) ¥²¶·¤j©ó 2.7959 * (£m1^2/n1 + £m2^2/n2)^0.5

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·í£m1^2 = 50 , £m2^2 = 50 ®É , ( £g1-£g2 ) ¥²¶·¤j©ó 3.47

·í£m1^2 = 100 , £m2^2 = 100 ®É ,( £g1-£g2 ) ¥²¶·¤j©ó 4.91

·í£m1^2 = 150 , £m2^2 = 150 ®É ,( £g1-£g2 ) ¥²¶·¤j©ó 6.02

·í£m1^2 = 200 , £m2^2 = 200 ®É ,( £g1-£g2 ) ¥²¶·¤j©ó 6.95

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METHODS FOR THE SEQUENTIAL PARALLEL COMPARISON DESIGN

cdr.lib.unc.edu/indexablecontent/uuid:035047ed-5f26-4cba-884d-b100959ab00d

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An analysis of adaptive design variations on the sequential parallel comparison design for clinical trials

www.ncbi.nlm.nih.gov/pmc/articles/PMC3612388/

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Interim analyses in an SPCD trial are conducted after a proportion (e.g., half) of the planned sample size has completed both stages of SPCD . It is desirable to conduct an interim look in order to check previous placebo response rates and treatment effect assumptions. Thus, if the previous assumptions were not correct, adaptations can be made to increase the power of the study.

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At the interim time, estimates of p1, q1, p2, and q2 were used to recalculate the sample size. If the new sample size exceeded the initial estimate, new patients were recruited to reach the target size. As with any sample-size re-estimation, it may not always be feasible to increase the sample size to the required level, and an upper bound must be placed.

If the new sample size exceeds the upper bound,then one can either discontinue the study out of futility and not test the hypotheses or continue with the planned trial to measure secondary outcomes of the study. If the planned sample size exceeds the new sample size, one can stop early and recover some of the cost of the study. However, Wittes and Brittain [12] cautioned that stopping a trial early may have a negative impact on the type I error rate and should be carefully evaluated.

( p1,the response rate of patients to drug during phase I;

p2, the response rate of patients to drug during phase II;

q1, the response rate of patients to placebo ¡V or a current standard treatment ¡V during phase I;

q2, the response rate of patients to placebo during phase II )

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t ²Î­p 2.369786793

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P ­È = 3.30035E-05 ( ¦Û¥Ñ«× 156 )

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Cinnamon Converts Poor Learning Mice to Good Learners: Implications for Memory Improvement

link.springer.com/article/10.1007%2Fs11481-016-9693-6

Abstract

This study underlines the importance of cinnamon, a commonly used natural spice and flavoring material, and its metabolite sodium benzoate (NaB) in converting poor learning mice to good learning ones. NaB, but not sodium formate, was found to upregulate plasticity-related molecules, stimulate NMDA- and AMPA-sensitive calcium influx and increase of spine density in cultured hippocampal neurons. NaB induced the activation of CREB in hippocampal neurons via protein kinase A (PKA), which was responsible for the upregulation of plasticity-related molecules. Finally, spatial memory consolidation-induced activation of CREB and expression of different plasticity-related molecules were less in the hippocampus of poor learning mice as compared to good learning ones. However, oral treatment of cinnamon and NaB increased spatial memory consolidation-induced activation of CREB and expression of plasticity-related molecules in the hippocampus of poor-learning mice and converted poor learners into good learners. These results describe a novel property of cinnamon in switching poor learners to good learners via stimulating hippocampal plasticity.

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·|­û¡G¤p©¯¹B10141538  µoªí®É¶¡:2018/12/27 ¤W¤È 10:38:44²Ä 1069 ½g¦^À³
Study Type : Interventional (Clinical Trial)

Estimated Enrollment : 348 participants

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Double (Participant, Investigator)

Primary Purpose: Treatment

Official Title: An Adaptive, Phase IIb/III, Multi-center, Prospective, Randomized, Double-Blind Placebo-controlled Study of the Safety and Efficacy of NaBen® (DAAO Inhibitor), as an Add-on Treatment for Schizophrenia in Adults

Actual Study Start Date : March 29, 2017

Estimated Primary Completion Date : December 31, 2018

Estimated Study Completion Date : June 30, 2019

-----------------------------------------------------------------------------------------------

¨Ì·Ó¹w­p§¹¦¨¤éEstimated Primary Completion Date : December 31, 2018

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·|­û¡G²q·Q10136148  µoªí®É¶¡:2018/12/20 ¤U¤È 06:31:58²Ä 1065 ½g¦^À³
Scientists create genomic resource to explore biological underpinnings of brain disorders

Date:

December 13, 2018

Source:

University of North Carolina Health Care

www.sciencedaily.com/releases/2018/12/181213142112.htm

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