Can We Delay the Progression of the Signs of Parkinson's Disease? The Dose-Response SPARX3 Trial

[Farooqji]

newswise.com/articles/resea...

[Farooqji]

sparx3pd.com/

[sharoncrayn]

excludes anyone on PD meds who has PD.

[jeffreyn in reply to sharoncrayn]

True. They are looking to recruit 370 persons diagnosed with Parkinson's disease who have not yet initiated dopaminergic therapy.

These PwPs will be randomly assigned to 2 groups: 1)60-65% HRmax or 2)80-85% HRmax, 4 times per week, 30 mins per session.

I may be wrong, but I reckon that it might be a struggle to get the 185 PwPs needed for group 2. Or, at least, to get those PwPs to the finish line (12 months).

clinicaltrials.gov/ct2/show...

[sharoncrayn in reply to jeffreyn]

I agree completely. 80-85% = running for 30x4. So you are very fit already, somehow diagnosed with PD, but no meds? Seems like a contradiction which means few and far between = a very small cohort.

[jeffreyn in reply to sharoncrayn]

I've had a look at the study record for the original SPARX trial. Two groups: 1)60-65% HRmax or 2)80-85% HRmax, 4 times per week, 128 PwPs, 6 months. The primary aim was "to determine whether individuals with de novo Parkinson's disease (naïve to drug treatment) can achieve the randomly assigned levels of mean exercise intensity (60-65% HRmax or 80-85% HRmax) and adhere to the exercise protocol."

It now seems to me that I was a little too pessimistic in my outlook.

clinicaltrials.gov/ct2/show...

Also, in the SPARX3 study record, the exercise activity of both groups is categorised as "treadmill walking". The word "running" does not appear anywhere in the study record.

[kevowpd in reply to jeffreyn]

Yeah i dont think it is that aspirational. I understand that with a suitable incline on the treadmill, 80% is probably achievable at a walking pace for many people (especially given that the exclusion criteria rules out people that are already doing a lot of exercise, i.e those that are likely to be fit and consequently require more work to get above 80%) and we arent talking about people with advanced PD here, by definition their PD will be mild.

I mean, i woudnt run it in Kodiak, Alaska, but anywhere with a big population within 30mins drive should manage.

[sharoncrayn in reply to jeffreyn]

Kev,

look at the results over 6 months.

I would say the results from the original sparx is "questionable." 1) No walking cohort was able to achieve a mean of 4 days per week (or above 3.2); 80% cohort was less than 3 days at 2.8. 2) Basically NO change in UPDRS mean score for the 80% cohort.

" I understand that with a suitable incline on the treadmill, 80% is probably achievable at a walking pace for many people"...I seriously doubt it. Cohort's average age = 64 and 50% female. So, you would need a 139-148 HR at 80-90% for 30 minutes assuming a RHR = 72. (Karvonen).

80-85% HR for 30 min x 4 days/wk for 64 year old person?...with PD?....Ain't going to happen very often.

Sharon

[kevowpd in reply to sharoncrayn]

I've read Schenkman's paper.

"an a priori hypothesized adherence of 3 days per week."

They hit 2.8 for the HI group. It wasnt far off where they thought they'd be. They also have the benefit of already doing it once, so i'd expect they'll have learned some lessons.

[jeffreyn in reply to sharoncrayn]

The 80-85% HRmax group contained 43 PwPs. For 38 of them, exercising on average 2.8 times per week, the mean value of their maximum-heart-rate percentages was 80.3 (78.8-81.7).

This means to me that the 80-85% HRmax target was achieved, and justifies going forward with a Phase 3 trial (i.e. SPARX3).

As kevowpd implies, the 2.8 figure is a bit of a red herring.

[sharoncrayn in reply to jeffreyn]

"The primary aim was "to determine whether individuals with de novo Parkinson's disease (naïve to drug treatment) can achieve the randomly assigned levels of mean exercise intensity (60-65% HRmax or 80-85% HRmax) and adhere to the exercise protocol."

they didn't do it per protocol. read the protocol. 4 days per week at 80-85% HR for 30 minutes(!). not just for few seconds or minutes. it isn't a peek effort; it is supposed to be continuous over 30.

What is the duration at 80-85% in minutes by participant? is the mean 1 minute for the cohort? 10? 20? anybody's guess.

change the protocol, obviously.

[jeffreyn in reply to sharoncrayn]

I agree that, in the study record for the original SPARX trial, the results section lacks sufficient detail.

The Schenkman paper has a lot more detail.

jamanetwork.com/journals/ja...

[sharoncrayn in reply to jeffreyn]

too bad they didn't do a better job in the CT.

the results showed 8-9 "AEs" in 80-85 group (n= 43) in the original results table. safe? almost 20% hit the deck one way or the other (4> than mild).

as I previously emphasized twice ----

"Treadmill exercise was prescribed for 4 days per week for 26 weeks with an a priori hypothesized adherence of 3 days per week. Included were 5 to 10 minutes of warm-up, 30 minutes of treadmill exercise at the target heart rate, and 5 to 10 minutes of cool down."

a full 30 minutes!? what % of 43 reached that level by week 4? why no #s? take a guess.

thanks for the link.

[MarionP]

They need a statistician, these groups are too small to achieve strong results unless this is a preliminary "proof of concept" phase that will be used to justify wider study. And if they have any fall-off during that year...

[sharoncrayn in reply to MarionP]

"compliance" with the protocols was questionable. Results info was too vague to draw any significant conclusion(s). Poorly reported (too bad).

[MarionP in reply to sharoncrayn]

Good way to put it. Doesn't hurt the general idea though, just means it wasn't tested very well...the underlying principle might indeed still have validity, just waiting to be shown by a few good studies, a little sturdier design...and would be a cheap solution for millions if it had some value, it's just behavior, very affordable.