BEE: Biology and Experience of Eating in Women With Obesity

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT02805972
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.2
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

The purpose of this study is to understand how the opioid system is involved in eating behavior.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Naloxone; Drug: Placebo	Phase 2

Detailed Description

Obesity is associated with greater risk for cardiovascular disease (CVD), stroke, diabetes, and mortality, and is a heterogeneous condition with various causes and thus a diversity of intervention targets. Compulsive overeating afflicts 30% of people seeking obesity treatment and increases risk for CVD factors. This trial involves two participant visits to test whether opioid blockade (Day 1 or 2, depending on randomization), compared to placebo (Day 1 or 2, depending on randomization), will elicit common symptoms of opioid withdrawal, including nausea. Participants will receive each condition on separate days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Biology and Experience of Eating in Women With Obesity
• Actual Study Start Date: May 20, 2017
• Actual Primary Completion Date: Jul 25, 2018
• Actual Study Completion Date: Jul 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Naloxone, then Placebo 4 mg / 0.1 ml Naloxone at visit 1, followed by 0.1 ml saline (Placebo) at visit 2 (with a washout period in between the two visits)	Drug: Naloxone; 4 mg / 0.1 ml; Other Names: Narcan ; Drug: Placebo; 0.1 ml; Other Names: saline
Experimental: Placebo, then Naloxone 0.1 ml saline (Placebo) at visit 1, followed by 4 mg / 0.1 ml Naloxone at visit 2 (with a washout period in between the two visits)	Drug: Naloxone; 4 mg / 0.1 ml; Other Names: Narcan ; Drug: Placebo; 0.1 ml; Other Names: saline

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Reported Nausea at 10 Minutes Post Treatment [10 minutes post-treatment]

   Dichotomized response on the "I feel nauseous" question of the Subjective Opiate Withdrawal Scale, at 10 minutes after the listed intervention (among participants who completed both intervention visits). Response 0 = absence of nausea, 1 = presence of nausea.

2. Number of Participants Who Reported Nausea at 30 Minutes Post Treatment [30 minutes post-treatment]

   Dichotomized response on the "I feel nauseous" question of the Subjective Opiate Withdrawal Scale, at 30 minutes after the listed intervention (among participants who completed both intervention visits). Response 0 = absence of nausea, 1 = presence of nausea.

Secondary Outcome Measures

1. Cortisol [25 minutes post-treatment]

   Geometric Mean Salivary Cortisol level.

2. Cortisol [55 minutes post-treatment]

   Geometric Mean Salivary Cortisol level.

3. Subjective Opiate Withdrawal Scale [10 minutes post-treatment]

   Summed score of Subjective Opiate Withdrawal Scale (SOWS). Scale consists of 16 items answered on a 5 point numeric rating scale. Score range is 0 (lesser withdrawal symptoms) to 64 (greater withdrawal symptoms). Scores were assessed at 10 minutes after Naloxone, and at a separate visit, 10 minutes after Placebo, among participants who completed both study visits.

4. Subjective Opiate Withdrawal Scale (Abbreviated) [30 minutes post-treatment]

   Mean score on subset of 5 items (which used a 5 point numeric rating response scale) from the Subjective Opiate Withdrawal Scale (SOWS). This summed score can range from 0 (corresponding to lesser withdrawal symptoms) to 20 (corresponding to greater withdrawal symptoms).

Other Outcome Measures

1. Reward-Driven Eating Scale (RED) [Evaluated before study visit 1]

   Reward-Driven Eating Scale (RED) total score ranges from 0 (lower reward-driven eating) to 52 (higher reward-driven eating).

2. Impulsivity (Delayed Discounting) [Impulsivity was assessed before the study visit 1 intervention.]

   Impulsivity, measured by the Delayed Discounting cognitive task, based on a series of 30 computer-administered trials or questions. Indifference points (a measure of how much a person values a delayed reward) are determined for time delays of: 1 day, 7 days, 30 days, 180 days, and 365 days, and these are used to calculate an Area Under the Curve which ranges from 0 to 1 (lower numbers indicate higher impulsivity) as a metric of probability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Obese, as defined by BMI greater than or equal to 30

• Self-reported binge eating as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), in the last 4 weeks

• If sexually active with men, must agree to use birth control until the final study visit is complete (e.g., barrier methods, oral contraceptive)

• Subject must be able to complete written informed consent procedures and be able to comply with the requirements of the study.

Exclusion Criteria:

• Pregnant or breastfeeding

• Severe hypotension (< 90/60 mmHg)

• Recent or current use of vasoconstrictor or vasodilator medication

• Current or history of diabetes

• Allergies to any ingredients in naloxone hydrochloride

• History of or current alcoholism or drug dependence

• Bulimia Nervosa as defined in DSM 5

• Current or past use of opiate-containing medications in the last 30 days

• Plan to use opiate-containing medications during study participation period

• Medical conditions that are contraindicated with intranasal procedures: Nasal septal abnormalities, nasal trauma, epistaxis, excessive nasal mucus, and intranasal damage caused by the use of substances (e.g., cocaine)

• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

• University of California, San Francisco

Investigators

• Principal Investigator: Ashley E Mason, PhD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 16, 2017
• Informed Consent Form - Jun 27, 2017

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02805972
• Other Study ID Numbers: 16-19392
• First Posted: Jun 20, 2016
• Last Update Posted: Nov 3, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of California, San Francisco: Obesity; Binge eating
• Additional relevant MeSH terms: Obesity; Naloxone

Study Results

Participant Flow

Arm/Group Title	Experimental: Naloxone, Then Placebo	Experimental: Placebo, Then Naloxone
Arm/Group Description	At the first intervention visit, participants were administered Naloxone, 4 mg / 0.1 ml, intranasally, after eating. After the washout period, at the second intervention visit, participants were administered the Placebo (saline), 0.1 ml, intranasally, after eating.	At the first intervention visit, participants were administered the Placebo (saline), 0.1 ml, intranasally, after eating. After the washout period, at the second intervention visit, participants were administered Naloxone, 4 mg / 0.1 ml, intranasally, after eating.
Period Title: Intervention Visit 1
STARTED	23	18
COMPLETED	23	18
NOT COMPLETED	0	0
Period Title: Intervention Visit 1
STARTED	23	18
COMPLETED	20	18
NOT COMPLETED	3	0
Period Title: Intervention Visit 1
STARTED	20	18
COMPLETED	20	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Naloxone, Then Placebo	Placebo, Then Naloxone	Total
Arm/Group Description	At visit 1, participants were administered Naloxone, 4 mg/ 0.1 ml, intranasally, after eating. After the washout period between visits, at visit 2, participants were administered the Placebo (saline), 0.1 ml, intranasally, after eating.	At visit 1, participants were administered the Placebo (saline), 0.1 ml, intranasally, after eating. After the washout period between visits, at visit 2, participants were administered Naloxone, 4 mg/ 0.1 ml, intranasally, after eating.	Total of all reporting groups
Overall Participants	23	18	41
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	18 100%	41 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.5 (6.5)	33.1 (6.5)	31.6 (6.5)
Sex: Female, Male (Count of Participants)
Female	23 100%	18 100%	41 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	3 16.7%	3 7.3%
Not Hispanic or Latino	23 100%	15 83.3%	38 92.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	0 0%	2 11.1%	2 4.9%
Asian or Pacific Islander	3 13%	0 0%	3 7.3%
White	16 69.6%	15 83.3%	31 75.6%
More than one race	4 17.4%	1 5.6%	5 12.2%
Region of Enrollment (Count of Participants)
United States	23 100%	18 100%	41 100%
Weight, kg (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	104.3 (23.9)	99.5 (17.0)	102.2 (21.1)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	38.1 (7.1)	36.4 (4.2)	37.3 (6.0)
Impulsivity (Probability) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Probability]	0.69 (0.21)	0.57 (0.29)	0.64 (0.25)
Reward-driven Eating (RED) scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	38.1 (6.1)	36.8 (5.2)	37.5 (5.7)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Reported Nausea at 10 Minutes Post Treatment
Description	Dichotomized response on the "I feel nauseous" question of the Subjective Opiate Withdrawal Scale, at 10 minutes after the listed intervention (among participants who completed both intervention visits). Response 0 = absence of nausea, 1 = presence of nausea.
Time Frame	10 minutes post-treatment

Outcome Measure Data

Analysis Population Description

All participants who received Naloxone, then Placebo, or Placebo, then Naloxone, by participating in both study intervention visits.

Arm/Group Title	Naloxone	Placebo
Arm/Group Description	4 mg / 0.1 ml naloxone Naloxone: 4 mg / 0.1 ml	0.1 ml saline Placebo: 0.1 ml
Measure Participants	38	38
Count of Participants [Participants]	17 73.9%	18 100%

2. Primary Outcome

Title	Number of Participants Who Reported Nausea at 30 Minutes Post Treatment
Description	Dichotomized response on the "I feel nauseous" question of the Subjective Opiate Withdrawal Scale, at 30 minutes after the listed intervention (among participants who completed both intervention visits). Response 0 = absence of nausea, 1 = presence of nausea.
Time Frame	30 minutes post-treatment

Outcome Measure Data

Analysis Population Description

All participants who received Naloxone, then Placebo, or Placebo, then Naloxone, by participating in both study intervention visits.

Arm/Group Title	Naloxone	Placebo
Arm/Group Description	4 mg / 0.1 ml naloxone Naloxone: 4 mg / 0.1 ml	0.1 ml saline Placebo: 0.1 ml
Measure Participants	38	38
Count of Participants [Participants]	13 56.5%	11 61.1%

3. Secondary Outcome

Title	Cortisol
Description	Geometric Mean Salivary Cortisol level.
Time Frame	25 minutes post-treatment

Outcome Measure Data

Analysis Population Description

Participants 25 minutes after Naloxone or Placebo administration, among those who completed both intervention visits

Arm/Group Title	Naloxone	Placebo
Arm/Group Description	Measurement of Cortisol here reported 25 min post Naloxone, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.	Measurement of Cortisol here reported 25 min post Placebo, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.
Measure Participants	38	38
Geometric Mean (Standard Deviation) [nmol/L]	3.22 (2.18)	3.37 (1.96)

4. Secondary Outcome

Title	Cortisol
Description	Geometric Mean Salivary Cortisol level.
Time Frame	55 minutes post-treatment

Outcome Measure Data

Analysis Population Description

Participants 55 minutes after Naloxone or Placebo administration, among those who completed both intervention visits

Arm/Group Title	Naloxone	Placebo
Arm/Group Description	Measurement of Cortisol here reported 55 min post Naloxone, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.	Measurement of Cortisol here reported 55 min post Placebo, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.
Measure Participants	38	38
Geometric Mean (Standard Deviation) [nmol/L]	3.61 (2.26)	2.90 (2.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Naloxone
	Comments	We compared cortisol values at 55 minutes, within person, across conditions. We Winsorized one participant's values for the placebo visit where values were between 2-4x above the 99th percentile value in the data and then log-transformed the data.
	Type of Statistical Test	Superiority
	Comments	The null hypothesis is that there would be no difference across the Naloxone and placebo conditions. The alternative hypothesis is that the cortisol value would be higher in the Naloxone condition than in the placebo condition.
Statistical Test of Hypothesis	p-Value	.067
	Comments	If the Winsorized value is excluded from analyses altogether, the P value is .012
	Method	t-test, 2 sided
	Comments	Cortisol was log transformed for the statistical test, and the reported mean difference was exponentiated back to the original units of nmol/L below.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Subjective Opiate Withdrawal Scale
Description	Summed score of Subjective Opiate Withdrawal Scale (SOWS). Scale consists of 16 items answered on a 5 point numeric rating scale. Score range is 0 (lesser withdrawal symptoms) to 64 (greater withdrawal symptoms). Scores were assessed at 10 minutes after Naloxone, and at a separate visit, 10 minutes after Placebo, among participants who completed both study visits.
Time Frame	10 minutes post-treatment

Outcome Measure Data

Analysis Population Description

Measurement of Subjective Opiate Withdrawal Scale here reported 10 min post Naloxone or 10 minutes after Placebo, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.

Arm/Group Title	Naloxone	Placebo
Arm/Group Description	Measurement of SOWS after Naloxone, among all participants who received Naloxone: 4 mg / 0.1 ml post eating at visit 1 and after a washout period, Placebo (saline): 0.1 ml post eating at visit 2, or were randomized to instead receive the same dosage of Placebo at visit 1 followed by a washout period and then Naloxone at visit 2.	Measurement of SOWS after Placebo, among all participants who received Naloxone: 4 mg / 0.1 ml post eating at visit 1 and after a washout period, Placebo (saline): 0.1 ml post eating at visit 2, or were randomized to instead receive the same dosage of Placebo at visit 1 followed by a washout period and then Naloxone at visit 2.
Measure Participants	38	38
Mean (Standard Deviation) [score on a scale]	5.67 (3.65)	5.03 (3.58)

6. Secondary Outcome

Title	Subjective Opiate Withdrawal Scale (Abbreviated)
Description	Mean score on subset of 5 items (which used a 5 point numeric rating response scale) from the Subjective Opiate Withdrawal Scale (SOWS). This summed score can range from 0 (corresponding to lesser withdrawal symptoms) to 20 (corresponding to greater withdrawal symptoms).
Time Frame	30 minutes post-treatment

Outcome Measure Data

Analysis Population Description

Measurement of the abbreviated SOWS here reported 30 min post Naloxone or 30 min post Placebo, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.

Arm/Group Title	Naloxone	Placebo
Arm/Group Description	Measurement of the abbreviated Subjective Opiate Withdrawal Scale here reported 30 min post Naloxone, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.	Measurement of the abbreviated Subjective Opiate Withdrawal Scale here reported 30 min post Placebo, among all participants who received Naloxone (4mg / 0.1 ml), then after a washout period, received Placebo (saline, 0.1 ml), or Placebo, then after a washout period, received Naloxone, by participating in both study intervention visits.
Measure Participants	38	38
Mean (Standard Deviation) [score on a scale]	1.42 (1.35)	1.53 (1.50)

7. Other Pre-specified Outcome

Title	Reward-Driven Eating Scale (RED)
Description	Reward-Driven Eating Scale (RED) total score ranges from 0 (lower reward-driven eating) to 52 (higher reward-driven eating).
Time Frame	Evaluated before study visit 1

Outcome Measure Data

Analysis Population Description

All eligible participants who were randomized to either order of intervention conditions.

Arm/Group Title	Experimental: Naloxone, Then Placebo	Placebo, Then Naloxone
Arm/Group Description	Includes all participants randomized to receive Naloxone (4mg / 0.1 ml), then after a washout period, receive Placebo (saline, 0.1 ml), with reward-driven eating evaluated before the first study intervention.	Includes all participants randomized to receive Placebo (saline, 0.1 ml), then after a washout period, receive Naloxone (4mg / 0.1 ml), with reward-driven eating evaluated before the first study intervention.
Measure Participants	23	18
Mean (Standard Deviation) [score on a scale]	38.1 (6.1)	36.8 (5.2)

8. Other Pre-specified Outcome

Title	Impulsivity (Delayed Discounting)
Description	Impulsivity, measured by the Delayed Discounting cognitive task, based on a series of 30 computer-administered trials or questions. Indifference points (a measure of how much a person values a delayed reward) are determined for time delays of: 1 day, 7 days, 30 days, 180 days, and 365 days, and these are used to calculate an Area Under the Curve which ranges from 0 to 1 (lower numbers indicate higher impulsivity) as a metric of probability.
Time Frame	Impulsivity was assessed before the study visit 1 intervention.

Outcome Measure Data

Analysis Population Description

All eligible participants randomized to either order of the intervention.

Arm/Group Title	Experimental: Naloxone, Then Placebo	Placebo, Then Naloxone
Arm/Group Description	Includes all participants randomized to receive Naloxone (4mg / 0.1 ml), then after a washout period, receive Placebo (saline, 0.1 ml), with reward-driven eating evaluated before the first study intervention.	Includes all participants randomized to receive Placebo (saline, 0.1 ml), then after a washout period, receive Naloxone (4mg / 0.1 ml), with reward-driven eating evaluated before the first study intervention.
Measure Participants	23	18
Mean (Standard Deviation) [Probability]	0.69 (0.21)	0.57 (0.29)

Adverse Events

Time Frame	Two days (each study intervention visit was conducted over approximately 4 hours, with the 2 interventions administered on a total of 2 separate visit days).
Adverse Event Reporting Description	The definition used did not differ from that of clinicaltrials.gov
Arm/Group Title	Naloxone, Then Placebo		Placebo, Then Naloxone
Arm/Group Description	Visit 1 intervention condition: 4 mg / 0.1 ml Naloxone, followed by visit 2 condition: 0.1 ml Placebo (saline)		Visit 1 intervention condition: 0.1 ml Placebo (saline), followed by visit 2 condition: 4 mg / 0.1 ml Naloxone
All Cause Mortality
	Naloxone, Then Placebo		Placebo, Then Naloxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/18 (0%)
Serious Adverse Events
	Naloxone, Then Placebo		Placebo, Then Naloxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Naloxone, Then Placebo		Placebo, Then Naloxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/18 (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.