Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03194516 |
| Other study ID # |
HP-00072961 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 12, 2017 |
| Est. completion date |
November 13, 2019 |
Study information
| Verified date |
April 2021 |
| Source |
University of Maryland, Baltimore |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Men with indolent forms of prostate cancer are managed expectantly using active surveillance,
with a goal of delaying treatment and its deleterious side effects. However, almost 50% of
men experience progression with this approach and require treatment. Elevated body mass index
(BMI) is associated with a dramatically increased risk of progression to higher grade
prostate cancer. The goal of the proposed research is to gather preliminary data evaluating
the effects of a promising dietary strategy to delay cancer progression in overweight and
obese prostate cancer patients undergoing active surveillance. The investigators hypothesize
that a ketogenic diet intervention may reduce BMI and favorably alter the prostate
microenvironment.
Description:
More than 1.6 million new cases of cancer are estimated in the United States in 2016, with
almost 600,000 individuals dying from the disease. Prostate cancer alone is responsible for
180,000 new diagnoses per year and remains the most common new cancer diagnosis for men.
Current treatment options for prostate cancer include surgery, radiation, high-intensity
focused ultrasound, and cryotherapy. Although typically successful, these strategies carry
significant risks for incontinence, erectile dysfunction, and local tissue injury. As a
result, for a select subgroup of men with more indolent forms of prostate cancer, active
surveillance has become the preferred management strategy. This approach entails periodic
laboratory testing, with prostate-specific antigen (PSA) checks at intervals of 3-6 months,
and repeat prostate biopsies every 1-2 years or earlier if indicated by PSA elevations.
Treatment interventions are typically withheld unless re-biopsy results indicate progression
to more aggressive disease. Prospective data comparing surgery and active surveillance have
demonstrated improved quality of life outcomes with the latter approach . Not surprisingly,
national registry data shows that active surveillance usage has increased from <15% between
1990 and 2009 to >40% between 2010 and 2013 for eligible patients . In order to ensure proper
patient selection for active surveillance, MRI guided confirmation biopsies have become
standard of care options. Almost one-third of patients will be found to harbor more
aggressive cancer than revealed by their initial biopsy. Ideally, treatment could be delayed
indefinitely for properly selected patients.
Although surveillance offers a reprieve from cancer treatment and its potential negative
sequelae, this benefit appears temporary for many men. Institutional cohort data indicate
that 36%-55% of men on active surveillance will require treatment for disease progression
within 10 years. One notable risk factor for disease progression during surveillance is
overweight and obesity. In a study of 565 prostate cancer patients on surveillance, a 50%
increased risk of pathologic progression was associated with every 5 kg/m2 increase in BMI
over 25. These results support additional evidence linking weight gain with an increased risk
of prostate cancer recurrence after surgery. They have also prompted studies examining
pre-surgical weight loss using caloric restriction to mitigate the risk associated with
obesity. A low carbohydrate, ketogenic approach has been previously studied in small samples
of patients with other types of cancer and also proposed for prostate cancer patients.
In brief, a ketogenic diet is a high-fat, low-carbohydrate diet that mimics the metabolic
state of long-term fasting. Ketone bodies are generated mainly by ketogenesis in the
mitochondrial matrix of liver cells and are subsequently exported via the blood to other
organs to cover the energy demands of cells throughout the body. Ketogenic deaminated amino
acids such as leucine also feed the citric acid cycle to form ketone bodies. Utilization of a
ketogenic diet as an adjuvant prostate cancer therapy is particularly intriguing given recent
preclinical data demonstrating that ketones function as endogenous histone deacetylase (HDAC)
inhibitors. HDAC inhibitors have been shown to inhibit prostate cancer proliferation in
preclinical models, and are already being studied in clinical trials. Therefore, the
ketogenic diet may have a direct impact on disease progression that may extend beyond the BMI
reduction achievable by caloric restriction, exercise or other weight loss strategies.
