Table 1.

Summary of recent clinical trials that are published or currently underway (https://clinicaltrials.gov, accessed on 3 June 2022).

N Patients	Recruitment Selection Strategy	Study Design	Primary Outcomes	Secondary Effects	Status
CoQ10
20	-Stable medication with carbidopa/LD, Selegiline and anticholinergic medication. -Symptoms of PD from 1–17 years. -54 to 70 years; All sexes	4 groups: CoQ10 provided at doses of 300, 600 or 1200 mg/day plus vitamin E (300 UI) and a placebo.	-↑ of plasma CoQ10 level -Normalize Complex I activity mitochondrial -↓ decrease in the original UPDRS score	Nonsignificant secondary effects	Phase 2 NCT00004731 Ref [45]
600	-Without PD medication before 60 days. -Presence of all cardinal signs within 5 years. -Hoehn and Yahr stage of 2.5 or less -30 years and older; All sexes	3 groups: CoQ10 at doses of 1200 and 2400 mg/day plus vitamin E (1200 UI) and placebo	No change in MDS-UPDRS score, Hoehn and Yahr score, PDQOL and SE-ADL scales.	-Back pain, -Constipation, -Anxiety, -Headache	Phase 3 NCT00740714 Ref [47]
72	-Stable PD medication for at least 4 weeks -18 years and older -All sexes	4 groups: Stratified by their genetic mitochondrial risk burden and randomized 1:1. CoQ10 at dose of 156 mg/day [QuinoMit Q10® Fluid] and placebo	Not reported	Not reported	Phase 2 DRKS00015880 Ref [55]
Urate/Inosine
298	-Without PD medication -Serum urate ≤ 5.7 mg/dL at 1st visit -Presence at least 2 of the cardinal signs -Hoehn and Yahr stage of 2.5 or less -30 years and older; All sexes	2 groups: Inosine at dose of 500 mg, 1 to 6 capsules per day to achieve serum urate at 7.1 to 8.0 mg/dL and placebo for 24 months	-No change in MDS-UPDRS score and DAT binding -↑ of serum urate level.	-Kidney stones	Phase 3 NCT00833690 Ref [73]
75	-Without PD medication -Serum urate ≤ 5.8 mg/dL at 1st visit -Presence at least 2 of the cardinal signs -30 years and older; All sexes	3 groups: Inosine at dose of 500 mg, 1 to 6 capsules per day to achieve serum urate at 6.1–7.0 mg/dL (mild), 7.1–8.0 mg/dL (moderate) and placebo for 2 years	-↓ significant decrease in the MDS-UPDRS score in moderate group in woman. -↑ plasma antioxidant capacity in woman. -↑ serum urate level and CSF in women	-Kidney stones	Phase 2 NCT02642393 Ref [195]
Glutathione/N-acetyl-cysteine
42	-Stable PD medication for at least 1 month -Hoehn and Yahr score of 1–2 inclusive -30 to 80 years -All sexes	2 groups: IV NAC at dose of 50 mg in 200 mL at frequency over one hour 1 × per week for 90 days plus Oral NAC at dose of 1200 mg/day and standard of care treatment (control group)	-↓ significant decrease in the MDS-UPDRS score -↑ DAT binding in caudate and putamen	Not reported	Not applicable NCT02445651 Ref [86]
8	-Stable PD medication -18 years and older -All sexes	2 groups: NAC at dose 6000 mg/day for 4 weeks and healthy controls	-↑ significant increase in catalase and GSH/GSSG peripheric -No change in 4–HNE and MDA. -No change in brain levels of GSH	-Gastrointestinal disorder -Nervous system disorders	Phase 2 NCT02212678 https://clinicaltrials.gov accessed on 3 June 2022
35	-Stable medication with monoamine oxidase inhibitor. -Diagnosis within the past 5 years -18 years and older; All sexes	2 groups: NAC at dose 2 g/day for 3 days and healthy controls	-↑ Cys–DA/DOPAC ratio	Not reported	Phase 1 NCT03104725 Ref [196]
47	-Without PD medication -50 to 75 years -All sexes	3 groups: NAC at dose of 1800 mg/day, 3600 mg daily and placebo for 30 days	Not reported	Not reported	Phase 2 NCT01470027 https://clinicaltrials.gov accessed on 3 June 2022
Vitamin C
67	-Stable medication with LD -64 years and older -All sexes	1 group: First time: 100 mg LD + 10 mg carbidopa and Second time (1 week later) 100 mg LD + 10 mg carbidopa + 200 mg AsA.	-↑ LD pharmacokinetics	Not reported	Not applicable Ref [98]
Vitamin E (Tocotrienols)
100	-Stable PD medication -Diagnosis within the past 1 year -PD of more than 1 year duration from diagnosis. -Hoehn and Yahr score ≥ 2 -40 to 90 years -All sexes	2 groups: Tocotrienols (400 mg/day) and placebo for 12 months	Not reported	Not reported	Phase 2 NCT04491383 https://clinicaltrials.gov accessed on 3 June 2022
Polyphenols
38	-Stable PD medication for at least 1 month. -Hoehn and Yahr score of 1–3 -30 years and older -All sexes	3 groups: EGCG at dose of 800 mg, dose of 1200 mg and placebo (mannitol) group for 4 weeks. Then one capsule twice daily for 4 weeks, and then one capsule three times daily for 40 weeks	-No change in UMSARS score	-Hepatotoxicity	Phase 3 NCT00461942 https://clinicaltrials.gov accessed on 3 June 2022
Herbal Medicine
30	-Stable PD medication -Initiation of PD symptoms in recent 6 years -Hoehn and Yahr score of ≤3 -30 to 80 years	2 groups: Oral Licorice at dose 10 cc/day and placebo (syrup) for 6 months	-↓ significant decrease in the MDS-UPDRS score -↓ daily activities score -↓ motor test score -No change in tremor, rigidity score and YAHR score.	-Nausea -Diarrhea -Urticaria	Not applicable Ref [197]
72	-Stable PD medication -Hoehn-Yahr score ≤4 -50 to 80 years; All sexes	2 groups: CSGs (Herbal cistanches 6 g, Polygonatum sibiricum 12 g, Salvia miltiorrhiza Bge. 15 g, Radix Paeoniae rubra 12 g, and Cortex Moutan 10 g), 2 capsules per day and placebo (Radix Bupleuri) for 12 weeks.	-↓ significative in the MDS-UPDRS sub-II score, -↓ significative in PDQ-39 score, -Significative improvement in CM syndrome score.	-Internal heat -Thirsty -Dryness heat.	ChiCTR-IOR-16008394 Ref [192]
107	-Basic treatment with prednisone. -Sleep disorder	2 groups: Huatan Jieyu granule and placebo for 4 weeks.	-↑ significative of total sleep time -↑ significative of NREM 2-3 -↑ significative of REM sleep -↓ significative in NREM1	Not reported	Not applicable Ref [193]
240	-Stable medication with carbidopa/LD, anticholinergics, MAO inhibitors, or amantadine for at least 28 days -Hoehn and Yahr stage score of ≤4 -NMSS score ≥40 -18 to 80 years; All sexes	2 groups: SQJZ herbal mixtures at dose of 29.375 g, 2 times per day and placebo for 12 weeks	Not reported	Not reported	Phase 2 NCT02616120 https://clinicaltrials.gov accessed on 3 June 2022

AsA: Ascorbic acid; CoQ₁₀: Coenzyme Q₁₀; CSF: cerebrospinal fluid; CSG: Congrong Shujing Granules; DAT: Dopamine transporter; DOPAC: 3,4- dihydroxyphenylacetic acid Cys 5-S-cysteinyl-dopamine; EGCG: Epigallocatechin gallate; IV: Intravenous; LD: Levodopa; MAO: Monoamine oxidase; MDS: Movement Disorder Society; NREM: Non rapid eye movement; NMSS: Non-Motor Symptoms Scale; NAC: N-acetyl-cysteine; PDQOL: Parkinson Disease Quality of Life; REM: Rapid eye movement; SE-ADL: Schwab and England -activities of daily living; UPDRS: original Unified Parkinson’s Disease Rating Scale; MDS-UPDRS: Muscle Disorder Society updated Unified Parkinson’s Disease Rating Scale; arrows correspond to: ↑: Increase; ↓: Decrease.