Coenzyme Q10 Phase 2

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Clifford Shults (University of California San Diego), Flint Beal (Weill Cornell), Richard Haas, Karl Kieburtz, David Oakes and colleagues in the Parkinson Study Group, a multicentre trial funded by the US National Institute of Neurological Disorders and Stroke (NINDS).

What happened

Coenzyme Q10 is a molecule that helps mitochondria (the cell's power plants) make energy and mops up damaging by-products; mitochondrial weakness had been linked to Parkinson's (landmark 11). The trial enrolled 80 people with early Parkinson's who did not yet need levodopa. They were randomised to placebo or coenzyme Q10 at 300, 600 or 1,200 mg a day, all taking vitamin E, for up to 16 months or until levodopa was needed. The measure was change in total UPDRS (a clinician's disability scale; higher is worse). Adjusted worsening was 11.99 points on placebo, 8.81 at 300 mg, 10.82 at 600 mg and 6.69 at 1,200 mg. The test for a dose trend gave P = 0.09, which the authors counted as meeting their prespecified criteria for a positive trend. Only 1,200 mg versus placebo reached P = 0.04, a prespecified secondary comparison. The drug was well tolerated.

Why it moved us toward a cure

It was the first controlled signal that a mitochondrial supplement might slow progression, and it led to the definitive trial, which tested 1,200 and 2,400 mg in landmark 26.

Outcome

Superseded. The result was modest, small and statistically fragile, and the authors asked for a larger trial. QE3 (600 people at 67 North American sites, 16 months, all on vitamin E) found no evidence of benefit at 1,200 or 2,400 mg a day (JAMA Neurology 2014). The episode is a standard case of a small Phase 2 "trend" not surviving a properly powered Phase 3. The same pattern recurred with exenatide (101, 20).

Sources

• Shults et al., Arch Neurol 2002;59(10):1541–1550, DOI 10.1001/archneur.59.10.1541 (PubMed 12374491) (numbers checked against the Europe PMC abstract)
• Weill Cornell press release, 2 Dec 2002
• Beal et al., QE3, JAMA Neurol 2014;71(5):543–552, DOI 10.1001/jamaneurol.2014.131
• Not yet verified: group sizes; whether the 600 mg result was ever explained; how much CoQ10 reaches the brain; the full text of the 2002 paper (abstract and press release only).