Targeted Disruption to Cancer Metabolism and Growth Through Dietary Macronutrient Modification
Primary Purpose
Ovarian Cancer, Endometrial Cancer
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Ketogenic diet
AND diet
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring ketogenic diet, carbohydrate-restricted diet
Eligibility Criteria
Inclusion Criteria:
- measurable disease or elevated CA-125
- classified as normal weight, overweight, or obese (BMI > 18.5)
- English speaking & reading
- can sign consent and are willing to be randomized and to adhere to the assigned protocol
Exclusion Criteria:
- pre-existing medical conditions that preclude enrollment: uncontrolled hypertension, myocardial infarction or cerebrovascular accident in the past six months, unstable angina within the last six months, congestive heart failure, serious infectious diseases, chronic hepatitis, cirrhosis, chronic malabsorption syndrome, chronic pancreatitis, chronic lung disease, major depressive or psychiatric disorder.
- current or medical condition that affects body weight such as uncontrolled hypo- or hyperthyroidism
- taking any of the following medications: anti-psychotic agents, monoamine oxidase inhibitors, antibiotics for HIV or tuberculosis, weight loss medications, or have taken weight loss medications in the last six months
- currently dieting
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Usual care plus ketogenic diet
Usual care plus AND diet
Arm Description
Outcomes
Primary Outcome Measures
change in fasting glucose
mg/dL
change in fasting insulin
uU/mL
change in fasting beta-hydroxybutyrate
mM
Secondary Outcome Measures
CA-125
U/mL
IGF-1
ng/mL
IGFBP-1
ug/mL
markers of inflammation
fasting serum concentrations of a variety of inflammatory markers
total body fat
g, measured by DXA and BIA
regional body fat
g, measured by DXA and BIA
total lean mass
g, measured by DXA and BIA
regional lean mass
g, measured by DXA and BIA
quality of life
Physical and mental health functioning as assessed by the Medical outcomes Study Short Form-12 Health Survey, which produces a physical component summary and mental component summary score.
perceived hunger
Perceived hunger assessed by a visual analog scale
food cravings
Cravings for particular types foods (fats, sweets, starches) as assessed by the Food Craving Inventory
lipids
fasting serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides
Full Information
NCT ID
NCT03171506
First Posted
May 22, 2017
Last Updated
August 8, 2017
Sponsor
University of Alabama at Birmingham
Collaborators
American Institute for Cancer Research
1. Study Identification
Unique Protocol Identification Number
NCT03171506
Brief Title
Targeted Disruption to Cancer Metabolism and Growth Through Dietary Macronutrient Modification
Official Title
Targeted Disruption to Cancer Metabolism Through Dietary Macronutrient Modification
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
November 9, 2015 (Actual)
Primary Completion Date
July 18, 2017 (Actual)
Study Completion Date
July 18, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
American Institute for Cancer Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this investigation is to examine the effects of 12 weeks of usual care plus a ketogenic diet (KD) or usual care plus dietary recommendations endorsed by the Academy of Nutrition and Dietetics (AND) in women with ovarian and endometrial cancer. Participants undergo testing at baseline and at 12 weeks; the testing consists of blood draws, questionnaires, and measures of body composition. The baseline visit also includes a meeting with a registered dietitian to discuss the guidelines of the assigned diet.
It is hypothesized that the KD group will have improved cancer outcome measures, beneficial body composition changes, reduced fasting concentrations of glucose and insulin, and higher ratings of patient satisfaction with the diet relative to the AND group.
Detailed Description
This investigation is a randomized, controlled clinical trial among 66 (for a final n of 50) women with ovarian and endometrial cancer. Patients are randomized to one of two study arms for 12 weeks: usual care plus the ketogenic diet (KD) or usual care plus dietary recommendations endorsed by the Academy of Nutrition and Dietetics (AND).
Cases are accrued in the University of Alabama at Birmingham gynecologic oncology clinic. Patients are then randomized to one of the two diet groups using a blocked randomization strategy. The prescription for the AND follows the Academy's 2013 guidelines, with modifications as necessary of ovarian cancer. The KD has a macronutrient composition of ~5% energy from carbohydrate, 25% energy from protein, and 70% energy from fat. Carbohydrate foods include non-starchy vegetables (e.g., salad greens, green beans, summer squash). Patients are advised to avoid refined starches and added sugar and to emphasize consumption of whole foods. Protein foods include meat, poultry, fish, and eggs. Because protein can be converted to glucose in the liver via gluconeogenesis, patients are counseled to eat no more than ~100g protein per day, distributed across the day. Fat-containing foods include olive, coconut, and nut oils; butter; tree nuts and nut butters; cheese; cream; coconut milk; and avocados. Patients are counseled to obtain the majority of their fat intake from mono-unsaturated fatty acids (e.g., olive oil), and medium-chain triglycerides (e.g., coconut oil and milk); from nuts and nut butters; and from fresh fish. Full-fat dairy is limited to 4 ounces of cheese per day; butter is not limited. This diet is formulated to be low glycemic and anti-inflammatory, thereby lowering glucose, insulin, and markers of inflammation. Total energy intake is not restricted, as the focus is on insulin reduction rather than weight loss.
Diet interventions are provided by registered dietitians at the University of Alabama at Birmingham. Participants meet one-on-one with a dietitian at the baseline testing visit. Patients record food intake such that the dietitian can review them on a weekly basis, provide feedback, and tailor nutrition counseling; said counseling is delivered via phone and e-mail on a weekly basis throughout the 12-week intervention. Food records are analyzed for macronutrient composition, a range of micronutrients, and glycemic index.
Outcome measures include demographics (age, sex, race); body composition by dual X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA); fasting concentrations of markers of inflammation, cancer progression (CA-125), and metabolism (glucose, insulin, ketones); cancer progression (as measured by CT scans done as part of usual care); quality of life (as measured by the Medical Outcomes Study Short Form-12 Health Survey, SF-12); satiety (as measured by a visual analog scale, VAS); and food cravings (as measured by the Food Craving Inventory, FCI).
Within groups changes in cancer markers, body composition, and other outcomes will be evaluated with paired t-tests. Between group differences will be evaluated with ANOVA/ANCOVA, controlling for relevant confounders (e.g., baseline values, age). Correlation analysis will be used to test the specific hypothesis that decrease in cancer outcomes across all patients will be associated with increase in serum ketone concentrations and decreasing concentration of fasting insulin. In a pilot study of 10 cancer patients, all of whom were placed on a KD, serum ketone production was increased to a greater extent (P<0.02) in those patients who showed remission or stable disease than in those patients who showed continued disease progression (Fine et al., 2012). Further, change in ketone production was associated with change in fasting insulin concentration. Thus, sample size calculations were based on change in fasting insulin using a previous diet intervention in a population of overweight/obese women with PCOS (Gower et al. 2013). In this study, a decrease in fasting insulin of 2.7 ± 4.6 µIU/ml was observed after 8 weeks of consumption of a eucaloric reduced-carbohydrate diet. Assuming a change of 2.7 ± 4.6 (µIU/ml), a two-sided paired t-test, and a significance alpha level of 0.05, we would have over 80% power to detect a significant change in fasting insulin with 25 participants per diet group. Allowing for 30% attrition, we plan to recruit 33 participants per diet group (total n=66).
Hypotheses include: 1) Cancer outcomes will improve in the KD group relative to the AND group, 2) The KD group will show a selective loss of visceral fat and preservation of lean mass, 3) Fasting concentrations of glucose, insulin, and insulin-like growth factor 1 (IGF-1) and its binding protein (IGFBP-1) will decline in the KD group but not in the AND group, 4) Changes in serum insulin concentration will be directly associated with changes in the cancer marker CA-125, 5) Changes in serum ketone concentration will be inversely associated with changes in cancer marker CA-125, and 6) Ratings of quality of life, food cravings, and satiety/hunger will improve in the KD group but not in the AND group.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Endometrial Cancer
Keywords
ketogenic diet, carbohydrate-restricted diet
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This study is a randomized clinical trial with a parallel arm design to evaluate the effects of 12 weeks of usual care plus AND or usual care plus KD on women with ovarian and endometrial cancer.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
57 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Usual care plus ketogenic diet
Arm Type
Experimental
Arm Title
Usual care plus AND diet
Arm Type
Placebo Comparator
Intervention Type
Other
Intervention Name(s)
Ketogenic diet
Intervention Description
Participants in the usual care plus ketogenic diet group will receive usual care plus dietary counseling in accordance with a ketogenic diet such that ~5% energy comes from carbohydrate, 25% energy from protein, and 70% energy from fat for the duration of the 12 week study.
Intervention Type
Other
Intervention Name(s)
AND diet
Intervention Description
Participants in the usual care plus AND diet group will receive usual care plus dietary counseling in accordance with the Academy of Nutrition and Dietetics guidelines in 2013 for the duration of the 12 week study.
Primary Outcome Measure Information:
Title
change in fasting glucose
Description
mg/dL
Time Frame
12 weeks
Title
change in fasting insulin
Description
uU/mL
Time Frame
12 weeks
Title
change in fasting beta-hydroxybutyrate
Description
mM
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
CA-125
Description
U/mL
Time Frame
baseline and 12 weeks
Title
IGF-1
Description
ng/mL
Time Frame
baseline and 12 weeks
Title
IGFBP-1
Description
ug/mL
Time Frame
baseline and 12 weeks
Title
markers of inflammation
Description
fasting serum concentrations of a variety of inflammatory markers
Time Frame
baseline and 12 weeks
Title
total body fat
Description
g, measured by DXA and BIA
Time Frame
baseline and 12 weeks
Title
regional body fat
Description
g, measured by DXA and BIA
Time Frame
baseline and 12 weeks
Title
total lean mass
Description
g, measured by DXA and BIA
Time Frame
baseline and 12 weeks
Title
regional lean mass
Description
g, measured by DXA and BIA
Time Frame
baseline and 12 weeks
Title
quality of life
Description
Physical and mental health functioning as assessed by the Medical outcomes Study Short Form-12 Health Survey, which produces a physical component summary and mental component summary score.
Time Frame
baseline and 12 weeks
Title
perceived hunger
Description
Perceived hunger assessed by a visual analog scale
Time Frame
baseline and 12 weeks
Title
food cravings
Description
Cravings for particular types foods (fats, sweets, starches) as assessed by the Food Craving Inventory
Time Frame
baseline and 12 weeks
Title
lipids
Description
fasting serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides
Time Frame
baseline and 12 weeks
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
This trial is limited to female participants, as it is a study of ovarian and endometrial cancer patients.
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
measurable disease or elevated CA-125
classified as normal weight, overweight, or obese (BMI > 18.5)
English speaking & reading
can sign consent and are willing to be randomized and to adhere to the assigned protocol
Exclusion Criteria:
pre-existing medical conditions that preclude enrollment: uncontrolled hypertension, myocardial infarction or cerebrovascular accident in the past six months, unstable angina within the last six months, congestive heart failure, serious infectious diseases, chronic hepatitis, cirrhosis, chronic malabsorption syndrome, chronic pancreatitis, chronic lung disease, major depressive or psychiatric disorder.
current or medical condition that affects body weight such as uncontrolled hypo- or hyperthyroidism
taking any of the following medications: anti-psychotic agents, monoamine oxidase inhibitors, antibiotics for HIV or tuberculosis, weight loss medications, or have taken weight loss medications in the last six months
currently dieting
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara A Gower, PhD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23444983
Citation
Gower BA, Chandler-Laney PC, Ovalle F, Goree LL, Azziz R, Desmond RA, Granger WM, Goss AM, Bates GW. Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS. Clin Endocrinol (Oxf). 2013 Oct;79(4):550-7. doi: 10.1111/cen.12175. Epub 2013 May 20.
Results Reference
background
PubMed Identifier
22840388
Citation
Fine EJ, Segal-Isaacson CJ, Feinman RD, Herszkopf S, Romano MC, Tomuta N, Bontempo AF, Negassa A, Sparano JA. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition. 2012 Oct;28(10):1028-35. doi: 10.1016/j.nut.2012.05.001. Epub 2012 Jul 26.
Results Reference
background
PubMed Identifier
30200193
Citation
Cohen CW, Fontaine KR, Arend RC, Soleymani T, Gower BA. Favorable Effects of a Ketogenic Diet on Physical Function, Perceived Energy, and Food Cravings in Women with Ovarian or Endometrial Cancer: A Randomized, Controlled Trial. Nutrients. 2018 Aug 30;10(9):1187. doi: 10.3390/nu10091187.
Results Reference
derived
PubMed Identifier
30137481
Citation
Cohen CW, Fontaine KR, Arend RC, Alvarez RD, Leath CA III, Huh WK, Bevis KS, Kim KH, Straughn JM Jr, Gower BA. A Ketogenic Diet Reduces Central Obesity and Serum Insulin in Women with Ovarian or Endometrial Cancer. J Nutr. 2018 Aug 1;148(8):1253-1260. doi: 10.1093/jn/nxy119.
Results Reference
derived
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Targeted Disruption to Cancer Metabolism and Growth Through Dietary Macronutrient Modification
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