PMID- 31608711
OWN - NLM
STAT- MEDLINE
DCOM- 20210303
LR  - 20210303
IS  - 2167-9223 (Electronic)
IS  - 2167-8421 (Linking)
VI  - 21
IP  - 1-2
DP  - 2020 Feb
TI  - Selection design phase II trial of high dosages of tamoxifen and creatine in 
      amyotrophic lateral sclerosis.
PG  - 15-23
LID - 10.1080/21678421.2019.1672750 [doi]
AB  - Objective: To conduct a phase-II trial using a ranking and selection paradigm 
      where multiple treatments are compared with limited sample size and the best is 
      chosen for a subsequent efficacy trial versus placebo. This strategy can find an 
      effective treatment faster than traditional strategy of conducting larger trials 
      against placebo. Methods: Sixty amyotrophic lateral sclerosis (ALS) participants 
      were randomized 1:1:1 to creatine 30 g/day (CRE), tamoxifen 40 mg/day (T40), or 
      tamoxifen 80 mg/day (T80), with matching placebo. The primary outcome was 38-week 
      change in ALS Functional Rating Scale-Revised (ALSFRS-R), analyzed in a 
      repeated-measures ANOVA. Secondary outcomes included slow vital capacity (SVC), 
      quantitative muscle strength, early drug discontinuation (EDD), adverse events 
      (AEs), and survival. Results: CRE participants experienced higher rates of 
      drug-related AEs (82% vs. 43% T40, 47% T80) and EDD (50% vs. 24% T40, 29% T80). 
      T80 participants experienced slower adjusted mean decline in ALSFRS-R in 
      points/month (-0.80 vs. -0.84 T40, -0.85 CRE) and quantitative muscle strength 
      but not in SVC and higher rates of mortality. Conclusion: Efficacy of T80 ranked 
      numerically superior to CRE and T40 with respect to ALSFRS-R decline. Following 
      the selection paradigm, T80 would be chosen to test against placebo. The approach 
      was not designed to distinguish among treatments that are nearly equally 
      effective or ineffective. If treatments are equivalent, then under the paradigm, 
      it does not matter which treatment is selected. Newer approaches for increasing 
      trial efficiency, including an adaptive platform trial design, may mitigate 
      limitations of the selection design.
FAU - Babu, Suma
AU  - Babu S
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
FAU - Macklin, Eric A
AU  - Macklin EA
AD  - Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, 
      Boston, MA, USA.
FAU - Jackson, Katherine E
AU  - Jackson KE
AD  - Office of the Prescription Drug Monitoring Program, Maryland Department of 
      Health, Baltimore, MD, USA.
FAU - Simpson, Elizabeth
AU  - Simpson E
AD  - McCance Center for Brain Health at Massachusetts General Hospital, Boston, MA, 
      USA.
FAU - Mahoney, Katy
AU  - Mahoney K
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
FAU - Yu, Hong
AU  - Yu H
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
FAU - Walker, Jason
AU  - Walker J
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
FAU - Simmons, Zachary
AU  - Simmons Z
AD  - Penn State Health Hershey Medical Center, Hershey, PA, USA.
FAU - David, William S
AU  - David WS
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
FAU - Barkhaus, Paul E
AU  - Barkhaus PE
AD  - Medical College of Wisconsin, Milwaukee, WI, USA.
FAU - Simionescu, Laura
AU  - Simionescu L
AD  - SUNY Upstate Medical Center, Syracuse, NY, USA.
FAU - Dimachkie, Mazen M
AU  - Dimachkie MM
AD  - University of Kansas Medical Center, Kansas City, KS, USA.
FAU - Pestronk, Alan
AU  - Pestronk A
AD  - Washington University School of Medicine, St. Louis, MO, USA.
FAU - Salameh, Johnny S
AU  - Salameh JS
AD  - American University of Beirut Medical Center, Beirut, Lebanon.
FAU - Weiss, Michael D
AU  - Weiss MD
AD  - University of Washington Medical Center, Seattle, WA, USA.
FAU - Brooks, Benjamin Rix
AU  - Brooks BR
AD  - Atrium Health Neurosciences Institute, Carolinas Medical Center, University of 
      North Carolina School of Medicine, Charlotte, NC, USA, and.
FAU - Schoenfeld, David
AU  - Schoenfeld D
AD  - Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, 
      Boston, MA, USA.
FAU - Shefner, Jeremy
AU  - Shefner J
AD  - Barrow Neurological Institute and University of Arizona College of Medicine, 
      Phoenix, AZ, USA.
FAU - Aggarwal, Swati
AU  - Aggarwal S
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
FAU - Cudkowicz, Merit E
AU  - Cudkowicz ME
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
FAU - Atassi, Nazem
AU  - Atassi N
AD  - Department of Neurology, Sean M Healey & AMG Center for ALS at Massachusetts 
      General Hospital, Neurological Clinical Research Institute, Boston, MA, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20191014
PL  - England
TA  - Amyotroph Lateral Scler Frontotemporal Degener
JT  - Amyotrophic lateral sclerosis & frontotemporal degeneration
JID - 101587185
RN  - 094ZI81Y45 (Tamoxifen)
RN  - MU72812GK0 (Creatine)
SB  - IM
CIN - Amyotroph Lateral Scler Frontotemporal Degener. 2020 Feb;21(1-2):3-4. PMID: 
      31661983
MH  - Adult
MH  - Aged
MH  - Amyotrophic Lateral Sclerosis/*drug therapy
MH  - Creatine/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Muscle Strength
MH  - Tamoxifen/*administration & dosage/*therapeutic use
MH  - Vital Capacity/drug effects/physiology
OTO - NOTNLM
OT  - Creatine
OT  - selection design
OT  - tamoxifen
OT  - trial
EDAT- 2019/10/15 06:00
MHDA- 2021/03/04 06:00
CRDT- 2019/10/15 06:00
PHST- 2019/10/15 06:00 [pubmed]
PHST- 2021/03/04 06:00 [medline]
PHST- 2019/10/15 06:00 [entrez]
AID - 10.1080/21678421.2019.1672750 [doi]
PST - ppublish
SO  - Amyotroph Lateral Scler Frontotemporal Degener. 2020 Feb;21(1-2):15-23. doi: 
      10.1080/21678421.2019.1672750. Epub 2019 Oct 14.