CompletedNCT02945410Updated Dec 19, 2019Results posted

Effect of Caloric Restriction and Protein Intake on Metabolism and Anabolic Sensitivity

An interventional study of Caloric Restriction and Protein in Weight Loss and Starvation, sponsored by University of Nebraska Lincoln. Completed at 1 site in United States. Open to male participants aged 19 Years to 30 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-12-19.

Sponsored by University of Nebraska Lincoln · Not applicable, Interventional, and Prevention

Phase: Not applicable
Study type: Interventional
Enrollment: 20
Allocation: Randomized
Ages: 19 Years to 30 Years
Sex: Male

Study summary

The purpose of this study is to determine if an increased protein intake can attenuate the suppression of metabolic and anabolic hormones during caloric restriction

Read the detailed description

Preliminary testing
Prior to the study start, participants will be weighed and body composition will be determined using calipermetry (7 sites) and bioelectrical impedance. Peak oxygen uptake (VO2peak) will be assessed using an incremental exercise test on a bicycle ergometer.
Randomization
Participants will proceed through each of the following conditions lasting 5 days:
CR-LP: Participants will be restricted to 30 kcal/kg FFM/day and protein intake will be low (0.8 g/kg BW/day).
CR-HP: Participants will be restricted to 30 kcal/kg FFM/day and protein intake will be high (1.7 g/kg BW/day).
CON: Participants will be in energy balance and consume 1.7 g protein/kg BW/day.
Diet Prescription
Dietary energy intake will be controlled using clinical products and maltodextrin to meet target energy intakes. Participants will received calcium and Vitamin D supplementation throughout the study.
Exercise Prescription
During all conditions, participants will conduct daily supervised exercise on a bicycle ergometer at an exercise intensity of 60% VO2peak. Exercise duration will be adjusted individually such that exercise energy expenditure will amount to 15 kcal/kg FFM/day. Additional exercise and intense physical activity will be prohibited.
Assessments
The following assessments will be conducted prior to the start of each condition as well as upon completion of each condition: body weight and composition (impedance), fasting blood draw for assessment of metabolic and anabolic hormones, resting metabolic rate, aerobic fitness (VO2peak), and questionnaires.
Washout

Once a participant has completed a study condition, participant will be allowed a washout of at least 14 days to allow protein balance to return to baseline (Hoffer \& Forse, 1990). During this time, participants will resume their regular diet and physical activity.

Conditions studied

Weight Loss
Starvation

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In context

Weight Loss

1,766 studies on the registry are indexed under Weight Loss; 277 are open to participants now.

This study's enrollment of 20 is below the median of 73 across 1,496 interventional studies indexed under Weight Loss.

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Lead sponsor

University of Nebraska Lincoln is the lead sponsor of 28 studies on the registry; 4 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 19 Years to 30 Years
Sexes eligible: Male
Accepts healthy volunteers: Yes

Inclusion criteria

4 hours/week of purposeful aerobic exercise over the last 3 months
Body mass index: 19-25 kg/m2
\< 15% body fat

Exclusion criteria

Exclusion Criteria:

Cardiovascular disease risk factors that would result in greater than low risk
Smoking
Type I, type II diabetes, or history of high fasting glucose;
History of high blood pressure and/or use of medication for hypertension;
History of Dyslipidemia, or on lipid-lowering medication;
Underlying health condition and/or use of medication that could interfere with any of our study outcomes.
History or current diagnosis of a clinical eating disorder
Failure to adhere to study protocol

Study design

Phase: Not applicable
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Single (Participant)
Enrollment: 20 participants (actual)

Study arms

Experimental
Caloric Restriction and High Protein
Participants will be calorie restricted to 30 kcal/kg FFM/day and consume 1.7 g protein/kg BW/day.
Other: Caloric Restriction · Other: Protein · Other: Exercise · Dietary Supplement: Calcium and Vitamin D · Other: Maltodextrin
Active comparator
Caloric Restriction and Normal Protein
Participants will be calorie restricted to 30 kcal/kg FFM/day and consume 0.8 g protein/kg BW/day.
Other: Caloric Restriction · Other: Exercise · Dietary Supplement: Calcium and Vitamin D · Other: Maltodextrin
Placebo comparator
Energy Balance
Participants will be in energy balance and consume 1.7 g protein/kg BW/day.
Other: Protein · Other: Exercise · Dietary Supplement: Calcium and Vitamin D · Other: Maltodextrin

Interventions

OtherCaloric Restriction
Participants will consume 30 kcal/kg FFM/day.
OtherProtein
Participants will consume 1.7 g protein/kg BW/day.
OtherExercise
Participants will conduct aerobic exercise designed to expend 15 kcal/kg FFM/day
Dietary supplementCalcium and Vitamin D
Participants will be provided calcium and vitamin D supplement in order to maintain calcium and Vitamin D intake constant across all study arms
OtherMaltodextrin
Participants will be provided with maltodextrin to supplement the liquid diet in order to meet caloric needs within each study arm

What researchers measure

Primary outcomes

Change in Resting Metabolic Rate
Time frame: Baseline and day 6
Change in Circulating IGF-1
Time frame: Baseline and day 6
Change in Marker of Bone Formation (P1NP)
Time frame: Baseline and day 6
Change in Marker of Bone Resorption (CTx)
Time frame: Baseline and day 6

Secondary outcomes

Change in Body Weight
Time frame: Baseline and day 6
Change in Body Fat Percentage
Time frame: Baseline and day 6
Change in Aerobic Fitness (VO2peak)
Analyzed in L/min rather than mL/kg/min to remove influence of weight loss.
Time frame: Baseline and day 6
Change in Perceived Hunger
Perceived hunger will be assessed using 0-100 visual analog scales. In this case, 100 means maximum hunger while 0 means minimal hunger.
Time frame: Baseline and day 6

Results

Posted Dec 19, 2019

Participant flow

Intervention 1 (5 Days)

Participant flow — Intervention 1 (5 Days)
Milestone	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP
Started	3	4	2	3	2	1
Completed	2	1	2	3	2	0
Not completed	1	3	0	0	0	1
Withdrew: Withdrawal by subject	0	3	0	0	0	0
Withdrew: Adverse event	1	0	0	0	0	1

Washout 1 (14 Days)

Participant flow — Washout 1 (14 Days)
Milestone	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP
Started	2	1	2	3	2
Completed	2	1	0	3	1
Not completed	0	0	2	0	1
Withdrew: Withdrawal by subject	0	0	2	0	1

Intervention 2 (5 Days)

Participant flow — Intervention 2 (5 Days)
Milestone	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP
Started	2	1	3	1
Completed	2	1	3	1
Not completed	0	0	0	0

Washout 2 (14 Days)

Participant flow — Washout 2 (14 Days)
Milestone	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP
Started	2	1	3	1
Completed	2	1	3	1
Not completed	0	0	0	0

Intervention 3 (5 Days)

Participant flow — Intervention 3 (5 Days)
Milestone	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP
Started	2	1	3	1
Completed	2	1	3	1
Not completed	0	0	0	0

Outcome measures

PrimaryChange in Resting Metabolic Rate

Time frame:: Baseline and day 6
Reported as:: Mean · kcal change

Change in Resting Metabolic Rate
kcal change	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Resting Metabolic Rate	-63.4 ± 58.2	-77.6 ± 100.1	-47.4 ± 41.7

PrimaryChange in Circulating IGF-1

Time frame:: Baseline and day 6
Reported as:: Mean · mol/L change

Change in Circulating IGF-1
mol/L change	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Circulating IGF-1	-2.3195714 ± 1.144509	-0.2107857 ± 2.369683	-1.1142857 ± 1.628160

PrimaryChange in Marker of Bone Formation (P1NP)

Time frame:: Baseline and day 6
Reported as:: Mean · % change

Change in Marker of Bone Formation (P1NP)
% change	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Marker of Bone Formation (P1NP)	3.73 ± 16.82	4.80 ± 19.78	-3.24 ± 8.95

PrimaryChange in Marker of Bone Resorption (CTx)

Time frame:: Baseline and day 6
Reported as:: Mean · % change

Change in Marker of Bone Resorption (CTx)
% change	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Marker of Bone Resorption (CTx)	0.24 ± 5.56	6.93 ± 16.51	-8.34 ± 10.41

SecondaryChange in Body Weight

Time frame:: Baseline and day 6
Reported as:: Mean · kg

Change in Body Weight
kg	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Body Weight	-2.3 ± 0.5	-2.1 ± 0.3	-0.0 ± 0.3

SecondaryChange in Body Fat Percentage

Time frame:: Baseline and day 6
Reported as:: Mean · % change

Change in Body Fat Percentage
% change	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Body Fat Percentage	-0.94 ± 0.23	-0.23 ± 0.41	-0.08 ± 0.53

SecondaryChange in Aerobic Fitness (VO2peak)

Analyzed in L/min rather than mL/kg/min to remove influence of weight loss.

Time frame:: Baseline and day 6
Reported as:: Mean · L/min change

Change in Aerobic Fitness (VO2peak)
L/min change	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Aerobic Fitness (VO2peak)	0.25 ± 0.08	0.01 ± 0.06	0.01 ± 0.12

SecondaryChange in Perceived Hunger

Perceived hunger will be assessed using 0-100 visual analog scales. In this case, 100 means maximum hunger while 0 means minimal hunger.

Time frame:: Baseline and day 6
Reported as:: Mean · units on a scale

Change in Perceived Hunger
units on a scale	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
Change in Perceived Hunger	18.4 ± 5.2	27.3 ± 11.9	10.3 ± 2.9

Adverse events

Collected over During the course of the entire study (~1.5 years).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Caloric Restriction and High Protein	0/11 (0%)	0/11 (0%)	1/11 (9.1%)
Caloric Restriction and Normal Protein	0/9 (0%)	0/9 (0%)	0/9 (0%)
Energy Balance	0/9 (0%)	0/9 (0%)	1/9 (11.1%)

Most frequent other events

Most frequent other events
Event	Caloric Restriction and High Protein	Caloric Restriction and Normal Protein	Energy Balance
NauseaGastrointestinal disorders	1/11	0/9	1/9

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
<=18 years	0	0	0	0	0	0	0
Between 18 and 65 years	3	4	2	3	2	1	15
>=65 years	0	0	0	0	0	0	0

Age, Continuous
Age, Continuous(Years)	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
Mean	21.3 ± 3.2	19.5 ± 0.6	21 ± 0	25.3 ± 3.8	27 ± 1.4	21 ± 0	22.3 ± 3.4

Sex: Female, Male
Sex: Female, Male(Participants)	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
Female	0	0	0	0	0	0	0
Male	3	4	2	3	2	1	15

Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
Count of participants	—	—	—	—	—	—	0

Region of Enrollment
Region of Enrollment(participants)	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
United States	3	4	2	3	2	1	15

Percentage Body Fat
Percentage Body Fat(% body fat)	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
Mean	17.9 ± 5.2	13.4 ± 4.4	12 ± 0.1	18 ± 1.7	19.2 ± 1.8	15 ± 0	15.9 ± 4.0

Aerobic Fitness (VO2max)
Aerobic Fitness (VO2max)(mL/kg/min)	(1) CRHP (2) EB (3) CRNP	(1) CRHP (2) CRNP (3) EB	(1) CRNP (2) EB (3) CRHP	(1) CRNP (2) CRHP (3) EB	(1) EB (2) CRHP (3) CRNP	(1) EB (2) CRNP (3) CRHP	Total
Mean	43.4 ± 2.1	46.7 ± 5.2	47.1 ± 6.5	41.0 ± 10.4	41.6 ± 5.0	42.3 ± 0	43.6 ± 5.7

Study locations

1 site

Sports and Exercise Nutrition Laboratory, Department of Nutrition and Health Sciences, Ruth Leverton Hall
Lincoln, Nebraska 68583, United States

References and documents

Publications

Hill JO. Understanding and addressing the epidemic of obesity: an energy balance perspective. Endocr Rev. 2006 Dec;27(7):750-61. doi: 10.1210/er.2006-0032. Epub 2006 Nov 22. PubMed 17122359 ↗
Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK; American College of Sports Medicine. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009 Feb;41(2):459-71. doi: 10.1249/MSS.0b013e3181949333. Erratum In: Med Sci Sports Exerc. 2009 Jul;41(7):1532. PubMed 19127177 ↗
Weinheimer EM, Sands LP, Campbell WW. A systematic review of the separate and combined effects of energy restriction and exercise on fat-free mass in middle-aged and older adults: implications for sarcopenic obesity. Nutr Rev. 2010 Jul;68(7):375-88. doi: 10.1111/j.1753-4887.2010.00298.x. PubMed 20591106 ↗
Forbes GB. Body fat content influences the body composition response to nutrition and exercise. Ann N Y Acad Sci. 2000 May;904:359-65. doi: 10.1111/j.1749-6632.2000.tb06482.x. PubMed 10865771 ↗
Areta JL, Burke LM, Camera DM, West DW, Crawshay S, Moore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG. Reduced resting skeletal muscle protein synthesis is rescued by resistance exercise and protein ingestion following short-term energy deficit. Am J Physiol Endocrinol Metab. 2014 Apr 15;306(8):E989-97. doi: 10.1152/ajpendo.00590.2013. Epub 2014 Mar 4. PubMed 24595305 ↗
Carbone JW, Pasiakos SM, Vislocky LM, Anderson JM, Rodriguez NR. Effects of short-term energy deficit on muscle protein breakdown and intramuscular proteolysis in normal-weight young adults. Appl Physiol Nutr Metab. 2014 Aug;39(8):960-8. doi: 10.1139/apnm-2013-0433. Epub 2014 Jun 19. PubMed 24945715 ↗
Wasserman DH, Kang L, Ayala JE, Fueger PT, Lee-Young RS. The physiological regulation of glucose flux into muscle in vivo. J Exp Biol. 2011 Jan 15;214(Pt 2):254-62. doi: 10.1242/jeb.048041. PubMed 21177945 ↗
Gault ML, Willems ME. Aging, functional capacity and eccentric exercise training. Aging Dis. 2013 Sep 25;4(6):351-63. doi: 10.14336/AD.2013.0400351. PubMed 24307968 ↗
Dulloo AG, Jacquet J, Montani JP, Schutz Y. How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats awaiting discovery. Obes Rev. 2015 Feb;16 Suppl 1:25-35. doi: 10.1111/obr.12253. PubMed 25614201 ↗
Wade GN, Schneider JE, Li HY. Control of fertility by metabolic cues. Am J Physiol. 1996 Jan;270(1 Pt 1):E1-19. doi: 10.1152/ajpendo.1996.270.1.E1. PubMed 8772468 ↗
Loucks AB. Energy balance and body composition in sports and exercise. J Sports Sci. 2004 Jan;22(1):1-14. doi: 10.1080/0264041031000140518. PubMed 14974441 ↗
Misra M, Klibanski A. The neuroendocrine basis of anorexia nervosa and its impact on bone metabolism. Neuroendocrinology. 2011;93(2):65-73. doi: 10.1159/000323771. Epub 2011 Jan 13. PubMed 21228564 ↗
Ihle R, Loucks AB. Dose-response relationships between energy availability and bone turnover in young exercising women. J Bone Miner Res. 2004 Aug;19(8):1231-40. doi: 10.1359/JBMR.040410. Epub 2004 Apr 19. PubMed 15231009 ↗
De Souza MJ, Williams NI. Beyond hypoestrogenism in amenorrheic athletes: energy deficiency as a contributing factor for bone loss. Curr Sports Med Rep. 2005 Feb;4(1):38-44. doi: 10.1007/s11932-005-0029-1. PubMed 15659278 ↗
Rizzoli R, Bianchi ML, Garabedian M, McKay HA, Moreno LA. Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone. 2010 Feb;46(2):294-305. doi: 10.1016/j.bone.2009.10.005. Epub 2009 Oct 17. PubMed 19840876 ↗
Pikosky MA, Smith TJ, Grediagin A, Castaneda-Sceppa C, Byerley L, Glickman EL, Young AJ. Increased protein maintains nitrogen balance during exercise-induced energy deficit. Med Sci Sports Exerc. 2008 Mar;40(3):505-12. doi: 10.1249/MSS.0b013e31815f6643. PubMed 18379214 ↗
Pasiakos SM, Margolis LM, McClung JP, Cao JJ, Whigham LD, Combs GF, Young AJ. Whole-body protein turnover response to short-term high-protein diets during weight loss: a randomized controlled trial. Int J Obes (Lond). 2014 Jul;38(7):1015-8. doi: 10.1038/ijo.2013.197. Epub 2013 Oct 29. PubMed 24166063 ↗
Chevalley T, Bonjour JP, Ferrari S, Rizzoli R. High-protein intake enhances the positive impact of physical activity on BMC in prepubertal boys. J Bone Miner Res. 2008 Jan;23(1):131-42. doi: 10.1359/jbmr.070907. PubMed 17892378 ↗
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan;96(1):53-8. doi: 10.1210/jc.2010-2704. Epub 2010 Nov 29. PubMed 21118827 ↗

Study documents

Protocol and statistical analysis plan · May 10, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Dec 19, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02945410
Lead sponsor: University of Nebraska Lincoln
Responsible party: Sponsor
First posted: Oct 26, 2016
Start date: Sep 2016
Primary completion: Feb 2019
Completion: Feb 2019
Results posted: Dec 19, 2019
Last update: Dec 19, 2019

Study contacts

Karsten Koehler, PhD

principal investigator · University of Nebraska Lincoln

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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