Vanderbilt early-DBS pilot

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

Mallory Hacker, David Charles and colleagues at Vanderbilt University Medical Center. Funded by the NIH (grants TR000445 and EB006136), the Michael J. Fox Foundation and Medtronic, which makes the DBS device. Five-year results in Neurology 2020;95:e393–e401.

What happened

DBS uses an implanted electrode to calm abnormal brain activity. It is approved for symptoms, and EARLYSTIM (landmark 140) showed quality-of-life gains in people with early motor complications. Vanderbilt asked a different question: does DBS also change the course?

• Design. NCT00282152. A prospective, single-blind pilot. 30 people (Hoehn & Yahr stage II off medication, on Parkinson's drugs for 0.5–4 years, no dyskinesia or fluctuations), enrolled 2006–2009, were randomised to optimal drug therapy alone or plus bilateral subthalamic-nucleus DBS. The registry shows 37 enrolled and the trial completed.
• Result at 5 years (28 people). DBS plus drugs needed a lower levodopa-equivalent daily dose (−240 mg, 95% CI −471 to −8; P=0.04). Odds of needing several Parkinson's drugs were 0.06 times those on drugs alone (95% CI 0.00 to 0.65; P=0.01). Odds of worse rest tremor were 0.21 times (95% CI 0.09 to 0.45; P<0.001). Safety was similar. Vanderbilt's release adds that drug-only patients were more than twice as likely to have clinically significant motor worsening, just short of significance.
• 11-year follow-up (Neuromodulation 2023;26:451–458). Only 12 of 29 people took part (4 DBS, 8 drugs-only; three drugs-only people had since had DBS). The DBS group had fewer motor complications (UPDRS IV, 3.5 points; P for interaction 0.03); other scores, quality of life and drug dose were comparable. The authors urged caution.
• Caution. The authors rated the evidence Class II and Vanderbilt said practice should not change. With 28–30 people, the trial can only suggest an effect.

Why it moved us toward a cure

If confirmed, it would be the first therapy to slow any part of Parkinson's. Even if not, it set up the first properly blinded test of "stimulation slows decline", and differences in tremor and drug need are measurable outcomes. See landmark 140.

Outcome

Open. The FDA has approved a pivotal multicentre trial (device exemption IDEG050016); Vanderbilt's 2020 release described it as 130 people, double-blind. I found no registry entry for that design. The related registered study NCT06008717 (sponsor Mallory Hacker; 40 planned; single-blind assessors; tests stimulation programming) is listed as not yet recruiting, with a start planned for January 2028.

Sources

• Hacker et al., Neurology 2020;95:e393–e401, doi:10.1212/WNL.0000000000009946 (abstract via Europe PMC, PMID 32601120)
• Hacker et al., Neuromodulation 2023, doi:10.1016/j.neurom.2022.10.051 (PMID 36567243)
• Vanderbilt University Medical Center news, 30 Jun 2020 · ClinicalTrials.gov NCT00282152 · NCT06008717 · MJFF grant page
• Not yet verified: the 2-year pilot report and its date; whether the 130-person pivotal trial is registered or enrolling; the drug-only motor-worsening odds ratio (press release only).