Gender Difference in Response to Caffeine in Children and Adolescents

• Sponsor: State University of New York at Buffalo (Other)
• Overall Status: Completed
• CT.gov ID: NCT02119416
• Collaborator: (none)
• Enrollment: 101
• Location: 1
• Arms: 3
• Duration (Months): 14
• Patients Per Site Per Month: 7.2

Study Details

Study Description

Brief Summary

Caffeine use is on the rise in America, and one of the most popular sources is soda. Among youth ages 8-16, caffeine consumption has increased by over 70% in the past 30 years. Few studies have examined the role of hormones in caffeine consumption within this age group.

The purpose of the current experiment was to determine the effect of caffeine on children 8 and 9 compared to those 15 and 16 years of age. The investigators were looking at the effect of puberty on the consumption of caffeine as well as the effect that the caffeine has on the body (for example: heart rate, blood pressure) and cognitive function.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Placebo Administration first; Drug: Low Caffeine Administration first (1mg/kg body weight); Drug: High Caffeine Administration first (2mg/kg body weight)	N/A

Detailed Description

Our previous studies have demonstrated sex differences in both the reinforcing properties of (Temple JL, Briatico LN, Clark EN, Dewey AM, 2009) and physiological responses to (Temple JL, Dewey AM, Briatico LN, 2010) caffeine. This is consistent with the literature on other types of drugs showing that men and women often differ in both drug self administration (Lynch WJ,2008 ) and drug sensitivity (Temple, JL, et al, 2008). These differences have been attributed, at least in part, to differences in gonadal hormones (Lynch WJ, 2008) ,Dreher JC et al, 2007). Our laboratory conducted a study investigating subjective effects of caffeine in post-pubertal adolescents and found that boys reported greater drug effects and liking of drug effects than did females (Temple JL, Dewey AM, Briatico LN, 2010, Temple JL, Ziegler AM,2011). In addition, the differences in feeling of the drug effects were related to salivary estradiol levels in females, but not in males, suggesting that steroid hormones can mediate the subjective effects of caffeine. When taken together, these data suggest that there are gender differences in acute and chronic effects of caffeine and that these differences may be mediated by differences in circulating steroid hormones. Previous studies have shown that subjective responses to caffeine vary across the menstrual cycle (Terner JM, de Wit H, 2006), with the greatest subjective effects occurring during the follicular phase, when estradiol levels begin to rise and peak just prior to the ovulatory LH surge. To date, no well-controlled studies have been conducted in humans examining the relationship between steroid hormones and caffeine effects on cognition, which the investigators will address in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Sex and Pubertal Stage Differences in Cardiovascular Responses to Caffeine in Children
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1mg/kg Caffeine Order of Caffeine Administration for Visits 1-6: 1mg, 2mg, 0mg, 1mg, 2mg, 0mg	Drug: Low Caffeine Administration first (1mg/kg body weight); On two of the 6 visits, participants received a placebo (flattened sprite) added to their beverage. Order of Caffeine Administration for Visits 1-6: 1mg, 2mg, 0mg, 1mg, 2mg, 0mg
Experimental: 2mg/kg caffeine Order of Caffeine Administration for Visits 1-6: 2mg, 0mg, 1mg, 2mg, 0mg, 1mg	Drug: High Caffeine Administration first (2mg/kg body weight); On two of the 6 visits, participants received a placebo (flattened sprite) added to their beverage. Order of Caffeine Administration for Visits 1-6: 2mg, 0mg, 1mg, 2mg, 0mg, 1mg
Experimental: Placebo Order of Administration for Visits 1-6: 0mg, 1mg, 2mg, 0mg, 1mg, 2mg	Drug: Placebo Administration first; All participants received each dose on two days and the order of administration was counterbalanced. Order of Administration for Visits 1-6: 0mg, 1mg, 2mg, 0mg, 1mg, 2mg

Outcome Measures

Primary Outcome Measures

1. Peak Heart Rate After 2 mg/kg of Caffeine [Heart rate was collected every 10 minutes for 60 minutes after the dose of caffeine.]

   Heart rate measurements were taken every 10 minutes, following 1 minute of rest with an automated Welch Allen Blood Pressure Cuff. We have reported the data as the peak heart rate after 2 mg/kg.

2. Peak Systolic Blood Pressure [Blood pressure was assessed every 10 minutes for 60 minutes after caffeine was administered.]

   Blood pressure measurements were taken every 10 minutes, following 1 minute of rest with an automated Welch Allen Blood Pressure Cuff. We have reported the peak heart rate after the 2 mg/kg dose of caffeine.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• males and females from 8-9 yoa or 15-17 yoa (post pubertal)

• those 8-9 much have Tanner Staging below 3

• those 15-17 much have Tanner Staging above 3.

• willing to come into the lab 6 times for 1.5-2 hours each

• those willing to abstain from consuming caffeine for 24 hours before each appointment

• those willing to withdraw from consuming anything other than water for 2 hours before each appointment.

• 15-17 year old females much have begun menarche

Exclusion Criteria:

• those on ADHD medication or other's impacting caffeine metabolism

• those reporting being on birth control or other hormones

• those that are pregnant or breastfeeding

• those outside the given age range or pubertal classification

• those reporting having an adverse effect of caffeine in the past

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	State University at New York at Buffalo	Buffalo	New York	United States	14214

Sponsors and Collaborators

• State University of New York at Buffalo

Investigators

• Principal Investigator: Jennifer L Temple, PhD, SUNY Buffalo
• Study Director: Amanda M Ziegler, MPH, SUNY Buffalo
• Study Director: Adam M Graczyk, MS, SUNY Buffalo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jennifer Temple, Principal Investigator, State University of New York at Buffalo
• ClinicalTrials.gov Identifier: NCT02119416
• Other Study ID Numbers: R01DA030386
• First Posted: Apr 21, 2014
• Last Update Posted: Aug 17, 2022
• Last Verified: Jul 1, 2022

• Keywords provided by Jennifer Temple, Principal Investigator, State University of New York at Buffalo: Cardiovascular influences; caffeine; healthy children
• Additional relevant MeSH terms: Caffeine

Study Results

Participant Flow

Arm/Group Title	1mg/kg Caffeine	2mg/kg Caffeine	Placebo
Arm/Group Description	Order of Caffeine Administration for Visits 1-6: 1mg/kg then 2mg/kg then 0mg/kg	Order of Caffeine Administration for Visits 1-6: 2mg/kg then 0mg/kg then 1mg/kg	Order of Administration for Visits 1-6: 0mg/kg then 1mg/kg then 2mg/kg
Period Title: Overall Study
STARTED	32	36	33
COMPLETED	30	35	31
NOT COMPLETED	2	1	2

Baseline Characteristics

Arm/Group Title	1mg/kg Caffeine	2mg/kg Caffeine	Placebo	Total
Arm/Group Description	Order of Caffeine Administration for Visits 1-6: 1mg/kg then 2mg/kg then 0mg/kg	Order of Caffeine Administration for Visits 1-6: 2mg/kg then 0mg/kg then 1mg/kg	Order of Administration for Visits 1-6: 0mg/kg then 1mg/kg then 2mg/kg	Total of all reporting groups
Overall Participants	30	35	31	96
Age (Count of Participants)
<=18 years	30 100%	35 100%	31 100%	96 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.2 (1.1)	12.2 (1.1)	12.2 (1.1)	12.2 (1.1)
Sex: Female, Male (Count of Participants)
Female	13 43.3%	17 48.6%	14 45.2%	44 45.8%
Male	17 56.7%	18 51.4%	17 54.8%	52 54.2%
Region of Enrollment (participants) [Number]
United States	30 100%	35 100%	31 100%	96 100%

Outcome Measures

1. Primary Outcome

Title	Peak Heart Rate After 2 mg/kg of Caffeine
Description	Heart rate measurements were taken every 10 minutes, following 1 minute of rest with an automated Welch Allen Blood Pressure Cuff. We have reported the data as the peak heart rate after 2 mg/kg.
Time Frame	Heart rate was collected every 10 minutes for 60 minutes after the dose of caffeine.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1mg/kg Caffeine Then 2 mg/kg Then 0 mg/kg	2mg/kg Caffeine Then 0 mg/kg Then 1 mg/kg	0 mg/kg Then 1 mg/kg Then 2 mg/kg
Arm/Group Description	Order of Caffeine Administration for Visits 1-6: 1mg/kg then 2mg/kg then 0mg/kg	Order of Caffeine Administration for Visits 1-6: 2mg/kg then 0mg/kg then 1mg/kg	Order of Administration for Visits 1-6: 0mg/kg then 1mg/kg then 2mg/kg
Measure Participants	30	35	31
Mean (Standard Error) [beats per minute]	73.6 (2.32)	73.2 (1.6)	79.6 (2.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1mg/kg Caffeine Then 2 mg/kg Then 0 mg/kg, 2mg/kg Caffeine Then 0 mg/kg Then 1 mg/kg, 0 mg/kg Then 1 mg/kg Then 2 mg/kg
	Comments
	Type of Statistical Test	Other
	Comments	Maximum heart rate after 2 mg/kg of caffeine compared to baseline was assessed using a mixed effects regression model. Sex and pubertal stage were included in the model as time invariant predictors.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	The p-value was not adjusted for multiple comparisons.
	Method	mixed effects regression
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1mg/kg Caffeine Then 2 mg/kg Then 0 mg/kg, 2mg/kg Caffeine Then 0 mg/kg Then 1 mg/kg, 0 mg/kg Then 1 mg/kg Then 2 mg/kg
	Comments	We used repeated measures ANOVAS and conducted planned comparisons between groups as post-hoc tests.
	Type of Statistical Test	Other
	Comments	We compared means of our dependent variables after administration of different doses of caffeine.
Statistical Test of Hypothesis	p-Value	< 0.05
	Comments	The p-value was set prior to the analysis and all comparisons were planned.
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Peak Systolic Blood Pressure
Description	Blood pressure measurements were taken every 10 minutes, following 1 minute of rest with an automated Welch Allen Blood Pressure Cuff. We have reported the peak heart rate after the 2 mg/kg dose of caffeine.
Time Frame	Blood pressure was assessed every 10 minutes for 60 minutes after caffeine was administered.

Outcome Measure Data

Analysis Population Description

Participants were randomized to a particular order, but this was a crossover design.

Arm/Group Title	1mg/kg Caffeine Then 2 mg/kg Than 0 mg/kg	2mg/kg Caffeine Than 0 mg/kg Than 1 mg/kg	0 mg/kg Than 1 mg/kg Than 2 mg/kg
Arm/Group Description	Order of Caffeine Administration for Visits 1-6: 1mg/kg then 2mg/kg then 0mg/kg	Order of Caffeine Administration for Visits 1-6: 2mg/kg then 0mg/kg then 1mg/kg	Order of Administration for Visits 1-6: 0mg, 1mg, 2mg, 0mg, 1mg, 2mg Placebo Administration first: All participants received each dose on two days and the order of administration was counterbalanced. Order of Administration for Visits 1-6: 0mg, 1mg, 2mg, 0mg, 1mg, 2mg
Measure Participants	30	35	31
Mean (Standard Error) [mmHg]	107.6 (1.82)	112.3 (1.69)	109.6 (2.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1mg/kg Caffeine Then 2 mg/kg Then 0 mg/kg, 2mg/kg Caffeine Then 0 mg/kg Then 1 mg/kg, 0 mg/kg Then 1 mg/kg Then 2 mg/kg
	Comments	order was included in the analysis. We examined caffeine dose.
	Type of Statistical Test	Other
	Comments	mixed effects regression models were used with sex and pubertal stage as time invariant predictors.
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	mixed effects regression
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	1mg/kg Caffeine Then 2 mg/kg Then 0 mg/kg, 2mg/kg Caffeine Then 0 mg/kg Then 1 mg/kg, 0 mg/kg Then 1 mg/kg Then 2 mg/kg
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	We collected adverse events over the five year period covered by this funding proposal.
Arm/Group Title	1mg/kg Caffeine		2mg/kg Caffeine		Placebo
Arm/Group Description	Order of Caffeine Administration for Visits 1-6: 1mg/kg then 2mg/kg then 0mg/kg		Order of Caffeine Administration for Visits 1-6: 2mg/kg then 0mg/kg then 1mg/kg		Order of Administration for Visits 1-6: 0mg/kg then 1mg/kg then 2mg/kg
All Cause Mortality
	1mg/kg Caffeine		2mg/kg Caffeine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/96 (0%)		0/96 (0%)
Serious Adverse Events
	1mg/kg Caffeine		2mg/kg Caffeine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/96 (0%)		0/96 (0%)
Other (Not Including Serious) Adverse Events
	1mg/kg Caffeine		2mg/kg Caffeine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/96 (0%)		0/96 (0%)		0/96 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.