PMID- 37550954
OWN - NLM
STAT- MEDLINE
DCOM- 20231110
LR  - 20231114
IS  - 1468-1331 (Electronic)
IS  - 1351-5101 (Linking)
VI  - 30
IP  - 12
DP  - 2023 Dec
TI  - A randomized, double-blind, placebo-controlled phase 2 study to assess safety, 
      tolerability, and efficacy of RT001 in patients with amyotrophic lateral 
      sclerosis.
PG  - 3722-3731
LID - 10.1111/ene.16020 [doi]
AB  - BACKGROUND AND PURPOSE: RT001 is a deuterated synthetic homologue of linoleic 
      acid, which makes membrane polyunsaturated fatty acids resistant to lipid 
      peroxidation, a process involved in motor neuron degeneration in amyotrophic 
      lateral sclerosis (ALS). METHODS: We conducted a randomized, multicenter, 
      placebo-controlled clinical trial. Patients with ALS were randomly allocated to 
      receive either RT001 or placebo for 24 weeks. After the double-blind period, all 
      patients received RT001 during an open-label phase for 24 weeks. The primary 
      outcome measures were safety and tolerability. Key efficacy outcomes included the 
      ALS Functional Rating Scale (ALSFRS-R), percent predicted slow vital capacity, 
      and plasma neurofilament light chain concentration. RESULTS: In total, 43 
      patients (RT001 = 21; placebo = 22) were randomized. RT001 was well tolerated; 
      one patient required dose reduction due to adverse events (AEs). Numerically, 
      there were more AEs in the RT001 group compared to the placebo group (71% versus 
      55%, p = 0.35), with gastrointestinal symptoms being the most common (43% in 
      RT001, 27% in placebo, p = 0.35). Two patients in the RT001 group experienced a 
      serious AE, though unrelated to treatment. The least-squares mean difference in 
      ALSFRS-R total score at week 24 of treatment was 1.90 (95% confidence interval = 
      -1.39 to 5.19) in favor of RT001 (p = 0.25). The directions of other efficacy 
      outcomes favored RT001 compared to placebo, although no inferential statistics 
      were performed. CONCLUSIONS: Initial data indicate that RT001 is safe and well 
      tolerated. Given the exploratory nature of the study, a larger clinical trial is 
      required to evaluate its efficacy.
CI  - (c) 2023 The Authors. European Journal of Neurology published by John Wiley & Sons 
      Ltd on behalf of European Academy of Neurology.
FAU - Weemering, Daphne N
AU  - Weemering DN
AUID- ORCID: 0009-0005-4182-3294
AD  - Department of Neurology, UMC Utrecht Brain Center, University Medical Center 
      Utrecht, Utrecht, the Netherlands.
FAU - Midei, Mark
AU  - Midei M
AD  - BioJiva, LLC, Los Altos, California, USA.
FAU - Milner, Peter
AU  - Milner P
AD  - BioJiva, LLC, Los Altos, California, USA.
FAU - Gopalakrishnan, Vidhya
AU  - Gopalakrishnan V
AD  - BioJiva, LLC, Los Altos, California, USA.
FAU - Kumar, Anil
AU  - Kumar A
AD  - BioJiva, LLC, Los Altos, California, USA.
FAU - Dannenberg, Andrew J
AU  - Dannenberg AJ
AD  - Emerald Bioventures, New York, New York, USA.
FAU - Bunte, Tommy M
AU  - Bunte TM
AD  - Department of Neurology, UMC Utrecht Brain Center, University Medical Center 
      Utrecht, Utrecht, the Netherlands.
FAU - Foucher, Juliette
AU  - Foucher J
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
AD  - Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, 
      Sweden.
FAU - Ingre, Caroline
AU  - Ingre C
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
AD  - Department of Neurology, ME Neurology, Karolinska University Hospital, Stockholm, 
      Sweden.
FAU - Kenina, Viktorija
AU  - Kenina V
AD  - Rare Neurological Disease Centre, Riga Stradins Clinical University Hospital, 
      Riga, Latvia.
AD  - Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia.
FAU - Rallmann, Karin
AU  - Rallmann K
AD  - Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
FAU - van den Berg, Leonard H
AU  - van den Berg LH
AUID- ORCID: 0000-0002-5203-9674
AD  - Department of Neurology, UMC Utrecht Brain Center, University Medical Center 
      Utrecht, Utrecht, the Netherlands.
FAU - van Eijk, Ruben P A
AU  - van Eijk RPA
AUID- ORCID: 0000-0002-7132-5967
AD  - Department of Neurology, UMC Utrecht Brain Center, University Medical Center 
      Utrecht, Utrecht, the Netherlands.
AD  - Biostatistics & Research Support, Julius Center for Health Sciences and Primary 
      Care, University Medical Center Utrecht, Utrecht, the Netherlands.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20230821
PL  - England
TA  - Eur J Neurol
JT  - European journal of neurology
JID - 9506311
RN  - 0 (RT001)
RN  - 0 (Linoleic Acids)
SB  - IM
MH  - Humans
MH  - *Amyotrophic Lateral Sclerosis/diagnosis
MH  - Linoleic Acids/therapeutic use
MH  - Double-Blind Method
MH  - Treatment Outcome
OTO - NOTNLM
OT  - RT001
OT  - amyotrophic lateral sclerosis
OT  - clinical trial
OT  - deuterated linoleic acid
OT  - lipid peroxidation
EDAT- 2023/08/08 06:42
MHDA- 2023/11/10 06:44
CRDT- 2023/08/08 01:23
PHST- 2023/07/20 00:00 [revised]
PHST- 2023/05/26 00:00 [received]
PHST- 2023/07/30 00:00 [accepted]
PHST- 2023/11/10 06:44 [medline]
PHST- 2023/08/08 06:42 [pubmed]
PHST- 2023/08/08 01:23 [entrez]
AID - 10.1111/ene.16020 [doi]
PST - ppublish
SO  - Eur J Neurol. 2023 Dec;30(12):3722-3731. doi: 10.1111/ene.16020. Epub 2023 Aug 
      21.