Evidence map›Paper›PMID 42467686›Full record

Trial reportPloS one2026

A phase III double-blind, placebo-controlled, randomized withdrawal trial of 5‑aminolevulinic acid hydrochloride with sodium ferrous citrate for efficacy and safety in patients diagnosed as Leigh syndrome.

Akira Ohtake, Yuichi Abe, Kei Murayama, Hideaki Shiraishi, Hitoshi Osaka, Satoko Kumada, Tetsuya Ito, Hidehito Kondo, Yusuke Hamada, Sayaka Suzuki-Ajihara and 13 more

Abstract readRandomized Controlled TrialClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Akira OhtakeDepartment of Pediatrics, Saitama Medical University Hospital, Moroyama, Japan.ORCID https://orcid.org/0000-0003-1147-3113
Yuichi AbeDepartment of Pediatrics, Saitama Medical University Hospital, Moroyama, Japan.ORCID https://orcid.org/0000-0003-3373-0029
Kei MurayamaDepartment of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Hideaki ShiraishiDepartment of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.
Hitoshi OsakaDepartment of Pediatrics, Jichi Medical University, Shimotsuke, Japan.
Satoko KumadaDepartment of Neuro Pediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Japan.
Tetsuya ItoDepartment of Pediatrics, Fujita Health University Hospital, Toyoake, Japan.
Hidehito KondoDepartment of Pediatrics, Japanese Red Cross Society Kyoto Daiichi Hospital, Kyoto, Japan.
Yusuke HamadaDepartment of Pediatrics, Toyonaka Municipal Hospital, Toyonaka, Japan.
Sayaka Suzuki-AjiharaDepartment of Pediatrics, Saitama Medical University Hospital, Moroyama, Japan.
Masato AraoDepartment of Pediatrics, Saitama Medical University Hospital, Moroyama, Japan.
Yuki UedaDepartment of Pediatrics, Hokkaido University Hospital, Sapporo, Japan.
Kohei NagaiDepartment of Pediatrics, Jichi Medical University, Shimotsuke, Japan.
Keiko IchimotoDepartment of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Ayako MatsunagaDepartment of Metabolism, Chiba Children's Hospital, Chiba, Japan.
Hirofumi KashiiDepartment of Neuro Pediatrics, Tokyo Metropolitan Neurological Hospital, Fuchu, Japan.
Yoko NakajimaDepartment of Pediatrics, Fujita Health University Hospital, Toyoake, Japan.
Hitoshi NakagawaDepartment of Clinical Development, SBI Pharmaceuticals, Minato, Tokyo, Japan.ORCID https://orcid.org/0009-0009-6568-9391
Shunichi KuroseDepartment of Clinical Development, SBI Pharmaceuticals, Minato, Tokyo, Japan.
Kaori FukudaDepartment of Clinical Development, SBI Pharmaceuticals, Minato, Tokyo, Japan.
Kiwamu TakahashiDepartment of Research and Development, SBI Pharmaceuticals, Minato, Tokyo, Japan.
Mitsugu YamauchiDepartment of Clinical Development, SBI Pharmaceuticals, Minato, Tokyo, Japan.
Motowo NakajimaDepartment of Clinical Development, SBI Pharmaceuticals, Minato, Tokyo, Japan.ORCID https://orcid.org/0000-0001-7687-6365

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveA phase III, double-blind, placebo-controlled, randomized withdrawal trial of SPP‑004 (5‑aminolevulinic acid hydrochloride and sodium ferrous citrate) was conducted to confirm the efficacy and safety of SPP-004 for maintenance of clinical response in patients diagnosed with Leigh syndrome (LS) showing central nervous system disorders.

methodsFifty-four patients entered a 24-week open-label period of SPP-004 administration. Among them, 28 patients who showed improvement on the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) for cranial nervous symptoms and myopathy symptoms proceeded to a 48-week double-blind (DB) period, where they were randomized (1:1) to receive SPP‑004 or placebo (n = 14 each). Efficacy was evaluated using NPMDS for the full analysis set (FAS) during the DB‑period (SPP-004 n = 13, Placebo n = 14) and the entire study period (n = 54). Safety evaluation focused on adverse events (AEs) in all 54 patients administered SPP-004.

resultsThe primary endpoint, the proportion of patients who discontinued due to inadequate efficacy at 48 weeks, was lower in the SPP-004 group (15.4% [95% CI: 1.9-45.4%]) compared to the placebo group (50.0% [23.0-77.0%]). Over 80% of the SPP-004 group showed maintained efficacy (p = 0.0486). All adverse drug reactions were mild, with no notable differences in AEs between groups.

conclusionThese findings suggest that SPP-004 is safe and may provide therapeutic effect for LS patients who achieved an initial clinical response.

Indexed as

Aminolevulinic AcidCitratesFerrous CompoundsLeigh DiseaseAdolescentChildChild, PreschoolCitric AcidDouble-Blind MethodFemaleHumansMaleTreatment OutcomeAminolevulinic AcidCitratesCitric Acidferrous citrateFerrous Compounds

Identifiers

PMID42467686
PMCPMC13379092

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.