Republican debate: A window on what happens when Donald Trump fades?

With a new front-runner, Wednesday night's debate could settle some big questions for the Republicans.

With Iowa caucuses less than 100 days away and the GOP field the most wide-open contest in at least a generation, expect the gloves to come off at Wednesday's Republican debate, where the focus will be on the economy and jobs.

Plenty has changed since the first two debates. Retired neurosurgeon Ben Carson has overtaken Donald Trump's longstanding prominence in the polls. Former Florida Gov. Jeb Bush, once considered the establishment pick, is struggling to hold onto first-tier status. Former Hewlett-Packard CEO Carly Fiorina surged and quickly faded. Wisconsin Gov. Scott Walker has dropped out. 

Can this debate in Boulder, Colo., which airs at 8 p.m. Eastern time on CNBC, change the course of the race? Here's what we'll be watching for:

How will Donald Trump handle being No. 2?

For the first time in months, a new national poll shows Mr. Trump, who has topped nearly every poll almost since he declared his candidacy in June, is not leading the Republican primary field.

From his wealth to his "Apprentice" and "Celebrity Apprentice" TV shows to his poll numbers and his "Make America Great Again" slogan, unchallenged superiority is at the core of Trump’s persona and his campaign. So what happens if he starts losing?

Expect the brash businessman to come out swinging at Wednesday night's debate. His main target? Probably the man who unseated his first-place ranking, Dr. Carson. 

How will Ben Carson react to attacks?

With a first-place finish in the latest polls, a brand new bestselling book, and plenty of attention from the press and supporters, Carson is on fire these days. But with prominence in the polls and the press comes scrutiny. Though he mostly went unchallenged in the last two debates, expect sharp attention on him tonight. 

Trump has already raised questions about Carson’s energy and his religion, suggesting his affiliation with the Seventh-day Adventist Church takes him out of the mainstream. Moderators will likely attempt to goad candidates, especially his direct competitors Trump and Sen. Ted Cruz, into attacking Carson. 

And Carson has given them plenty of ammunition recently by staking some controversial positions: he has suggested the Holocaust could have been avoided if Jews in Germany had guns, he likened women who have abortions to slaveowners, and said Muslims should be barred from becoming president.

But whatever questions or challenges come his way, Carson has said he won't "get in the mud pit."

Can Jeb Bush reinvigorate his candidacy?

Though he was once the Republican establishment favorite, the former Florida governor has dropped to fourth place in the Real Clear Politics average of polls. He trails novices Trump, Carson, and his mentee, Florida Sen. Marco Rubio. 

His poll numbers are sagging, his fundraising has been lackluster recently, he has downsized his staff, and attacks on his energy level and enthusiasm seem to be sticking. 

If he wants to stay in the race, Governor Bush needs to deliver a game-changing performance Wednesday night. The only problem? He's an awkward debater who's more comfortable talking policy than delivering zingers. 

Nonetheless, he needs to show he still has the fire in his belly, said Katie Packer, deputy campaign manager for Mitt Romney's 2012 campaign, to CNN. 

"He needs to have a performance that stands out from the crowd. He won't be center stage this time so he need to, in words and actions, figure out how not to fade into the wings," she said.

Can Carly Fiorina break through again? 

Ms. Fiorina rocketed from a little-known, outsider candidate who polled so low she was relegated to the undercard debate to one of the party's top contenders, thanks to standout debate performances in August and September, as The Christian Science Monitor reported Tuesday.

But then she faded. After her well-reviewed September debate performance, Fiorina polled at 15 percent, according to a CNN/ORC national survey, but now, she's fallen back to 4 percent in the same survey. 

Wednesday evening may be her make-or-break opportunity. 

"The debate is essential because without a good debate performance, she’s history," Republican strategist John Feehery told The Hill. 

The problem? The debate is focused on job creation, which may be a tough subject for even a skilled communicator like Fiorina. As CEO of Hewlett-Packard, she oversaw the layoffs of 30,000 employees.

When will bottom-tier candidates start to drop out?

Despite the number of consistently low-polling candidates and the ever-approaching Iowa caucuses, the GOP field remains remarkably full. With 15 candidates still in the mix, it is the most wide-open GOP contest in at least a generation. 

Undercard debaters – former Pennsylvania Sen. Rick Santorum, Louisiana Gov. Bobby Jindal, former New York Gov. George Pataki, and South Carolina Sen. Lindsey Graham – are consistently polling below 3 percent, and even prime-time debaters former Arkansas Gov. Mike Huckabee, New Jersey Gov. Chris Christie, former Ohio Gov. John Kasich, and Kentucky Sen. Rand Paul poll around 3 percent. (Virginia Gov. Jim Gilmore polls so low he hasn't yet qualified to participate in any debate.)

Most are also struggling to raise funds and stay afloat, yet they're all hanging on. 

"That’s been one of the most striking parts to me about this year – how many candidates have insisted on staying in the race," said New York Times national political correspondent Jonathan Martin. 

Everyone seems to be counting down the clock on Trump and Carson, in the hopes that their lead in the polls will eventually run out – and waiting to discover what will happen when they fade. 

This debate could mark the tipping point for the Republican field.