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. 2019 Aug 20;18(6):e13031. doi: 10.1111/acel.13031

Table 1.

Summary of antioxidant clinical trials for Parkinson's disease

Authors Study design Participants Intervention/duration Redox modulation Outcome measures Status/results
The Parkinson Study Group and DATATOP study (1993) DPRCT 800 early PD patients, within 5 years of diagnosis

  • 2‐year intervention

  • Randomization

    1. Deprenyl (10 mg/day)

    2. α‐tocopherol (2,000 IU/day)

    3. Deprenyl/α‐tocopherol

    4. Placebo

 Deprenyl—reduced toxin‐induced ●OH− formation (Wu, Chiueh, Pert, & Murphy, 1993), and iron‐induced oxidative stress (Budni et al., 2007). α‐Tocopherol—lipophilic ROS scavenger, reduced lipid peroxidation (Niki, 2015) The onset of disability prompting levodopa administration Complete—no evidence of clinical benefit
Shults et al. (2002) DPRCT 80 early PD patients who did not require treatment for their disability

  • 16‐month intervention

  • Randomization

    1. Coenzyme Q (300 mg/day)

    2. Coenzyme Q (600 mg/day)

    3. Coenzyme Q (1,200 mg/day)

    4. Placebo

 Coenzyme Q—lipophilic ROS scavenger, reduces lipid peroxidation (Bentinger, Brismar, & Dallner, 2007) Safety and tolerability, UPDRS score Complete –safe and tolerable up to 1,200 mg/day, appeared to slow progression of PD motor impairment
The Parkinson Study Group DPRCT 600 early PD patients, within 5 years of diagnosis

  • 16‐month intervention

  • Randomization

    1. Coenzyme Q (1,200 mg/day)

    2. Coenzyme Q (2,400 mg/day)

    3. Placebo

  • Each group combined with α‐tocopherol (1,200 IU/day)

 Coenzyme Q and α‐Tocopherol as above UPDRS score Complete—no evidence of clinical benefit
Snow et al. (2010), Protect Study Group DPRCT 128 early PD patients who do not require treatment for their disability

  • 12‐month intervention

  • Randomization

    1. MitoQ (40 mg/day)

    2. MitoQ (80 mg/day)

    3. Placebo

 MitoQ—a coenzyme Q mimetic, mitochondria‐targeted ROS scavenging (Tauskela, 2007) UPDRS score Complete—no evidence of clinical benefit
NET‐PD investigators DPRCT 1,741 early PD patients, within 5 years of diagnosis

  • 5‐ to 8‐year intervention

  • Randomization

    1. Creatine (10g/day)

    2. Placebo

 Creatine—induction of antioxidant enzymes (TRx, PRx), effective scavenger of ●OH− and O2 −, protects against mitochondrial DNA and RNA (Sestili et al., 2011) Modified Rankin Scale, Symbol Digit Modalities Test, PDQ−39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity Terminated early for futility—no evidence of clinical benefit
Mischley, Lau, Shankland, Wilbur, and Padowski (2017) DPRCT 45 early PD patients (H&Y stage 1–3)

  • 3‐month intervention

  • Randomization

    1. GSH (300 mg IN/day)

    2. GSH (600 mg IN/day)

    3. Placebo

 GSH—low molecular weight antioxidant; ROS detoxification, redox signaling molecule, substrate for antioxidant enzyme pathways (Forman, Zhang, & Rinna, 2009) UPDRS Completed—no evidence of clinical benefit
Hauser, Lyons, McClain, Carter, and Perlmutter (2009) DPRCT 21 PD patients (H&Y stage 2–5), nonresponsive to L‐DOPA

  • 4‐week intervention

  • Randomization

    1. GSH (1,400 mg IV, 3×/week)

    2. Placebo

 GSH as above Safety and tolerability, UPDRS Completed—safe and tolerable up to 4,200 mg/week, no preliminary evidence of clinical benefit
NINDS Exploratory Trials in Parkinson Disease DPRCT 210 early PD patients, within 5 year of diagnosis (H&Y stage 1–2)

  • 44‐week intervention

  • Randomization

    1. Pioglitazone (15 mg/day)

    2. Pioglitazone (45 mg/day)

    3. Placebo

 Pioglitazone—induction of peroxisomal and cytosol antioxidant proteins (SOD1, catalase, GPx1; Filograna et al., 2016) UPDRS Completed—no evidence of clinical benefit
Weill Medical College of Cornell University (NCT01470027) Parallel assignment DPRCT 30 PD patients, less than 15 years postdiagnosis

  • 4‐week intervention

  • Randomization

    1. N‐acetyl‐cysteine (1,800 mg/day)

    2. N‐acetyl‐cysteine (3,600 mg/day)

    3. Placebo

 N‐acetyl‐cysteine—ROS scavenger and major substrate for GSH/GPx antioxidant pathway (Firuzi et al., 2011) UPDRS, Cerebral GSH levels (measured by Proton Magnetic Resonance Spectroscopy) Completed—results yet to be published
NINDs, Michael J. Fox Foundation, The Parkinson Study Group (NCT02168842) Parallel assignment DPRCT 336 early PD patients, within 3 years of diagnosis (H&Y stage 1–2)

  • 3‐year intervention

  • Randomization

    1. Isradipine (10 mg/day)

    2. Placebo

 Isradipine—Calcium channel antagonist, reduction in mitochondrial ROS production by reducing calcium‐buffering burden (Rodnitzky, 1999) UPDRS Active—results yet to be published
Martin‐Bastida et al. (2017) DPRCT 22 early PD patients, within 5 years of diagnosis (H&Y stage 1–2)

  • 6‐month intervention

  • Randomization

    1. Deferiprone (20 mg kg day−1)

    2. Deferiprone (30 mg kg day−1)

    3. Placebo

 Deferiprone—effective iron chelator, reduces iron‐mediated ROS generation (Hare & Double, 2016) Safety and tolerability, UPDRS, brain iron concentrations assessed by T2* MRI Completed—safe and tolerable up to 30 mg kg day−1, no evidence of clinical benefit
FAIR PARK II (NCT02655315) Parallel assignment DPRCT 338 early PD patients, within 18 months of diagnosis, (H&Y stage 1–3)

  • 9‐month intervention

  • Randomization

    1. Deferiprone (30 mg kg day−1)

    2. Placebo

 Deferiprone as above UPDRS Recruiting
Collaborative Medicinal Development Pty Limited (NCT03204929) Single group assignment, open label dose escalation 38 PD patients (estimated), within 5 years of diagnosis (H&Y stage 1–2)

  • 6‐month intervention of Cu(II)‐atsm

  • Dose escalation (starting 12 mg/day) to determine RP2D. Phase 2—expansion cohort (n = 20 patients) treated with RP2D until 6 months

 Cu(II)‐atsm—reduction of cellular ROS and peroxynitrite, largely unknown mechanism, promotion of SOD1 antioxidant activity (Hung et al., 2012) Safety and tolerability – patients in each dose cohort with intolerance up to 6 months treatment, UPDRS Recruiting

Abbreviations: DPRCT, double‐blind, placebo‐controlled, randomized clinical trial; H&Y, Hoehn and Yahr; PD, Parkinson's disease; UPDRS, Unified Parkinson's Disease Rating Scale.