Obesity
Conditions
Keywords
Obesity, Binge eating
Brief summary
The purpose of this study is to understand how the opioid system is involved in eating behavior.
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.
Interventions
DRUGNaloxone
4 mg / 0.1 ml
DRUGPlacebo
0.1 ml
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| Cortisol | 25 minutes post-treatment | Geometric Mean Salivary Cortisol level. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naloxone, Then Placebo 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. | 23 |
| Placebo, Then Naloxone 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. | 18 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | Naloxone, Then Placebo | Total | Placebo, Then Naloxone |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 41 Participants | 18 Participants |
| Age, Continuous | 30.5 years STANDARD_DEVIATION 6.5 | 31.6 years STANDARD_DEVIATION 6.5 | 33.1 years STANDARD_DEVIATION 6.5 |
| Body Mass Index (BMI) | 38.1 kg/m^2 STANDARD_DEVIATION 7.1 | 37.3 kg/m^2 STANDARD_DEVIATION 6 | 36.4 kg/m^2 STANDARD_DEVIATION 4.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 38 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Impulsivity | 0.69 Probability STANDARD_DEVIATION 0.21 | 0.64 Probability STANDARD_DEVIATION 0.25 | 0.57 Probability STANDARD_DEVIATION 0.29 |
| Race/Ethnicity, Customized Asian or Pacific Islander | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized More than one race | 4 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 31 Participants | 15 Participants |
| Region of Enrollment United States | 23 Participants | 41 Participants | 18 Participants |
| Reward-driven Eating (RED) scale | 38.1 units on a scale STANDARD_DEVIATION 6.1 | 37.5 units on a scale STANDARD_DEVIATION 5.7 | 36.8 units on a scale STANDARD_DEVIATION 5.2 |
| Sex: Female, Male Female | 23 Participants | 41 Participants | 18 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight, kg | 104.3 kilograms STANDARD_DEVIATION 23.9 | 102.2 kilograms STANDARD_DEVIATION 21.1 | 99.5 kilograms STANDARD_DEVIATION 17 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 18 |
| other Total, other adverse events | 0 / 23 | 0 / 18 |
| serious Total, serious adverse events | 0 / 23 | 0 / 18 |
Outcome results
Primary
Number of Participants Who Reported Nausea at 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.
Time frame: 10 minutes post-treatment
Population: All participants who received Naloxone, then Placebo, or Placebo, then Naloxone, by participating in both study intervention visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Naloxone | Number of Participants Who Reported Nausea at 10 Minutes Post Treatment | 17 Participants |
| Placebo | Number of Participants Who Reported Nausea at 10 Minutes Post Treatment | 18 Participants |
Primary
Number of Participants Who Reported Nausea at 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.
Time frame: 30 minutes post-treatment
Population: All participants who received Naloxone, then Placebo, or Placebo, then Naloxone, by participating in both study intervention visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Naloxone | Number of Participants Who Reported Nausea at 30 Minutes Post Treatment | 13 Participants |
| Placebo | Number of Participants Who Reported Nausea at 30 Minutes Post Treatment | 11 Participants |
Secondary
Cortisol
Geometric Mean Salivary Cortisol level.
Time frame: 25 minutes post-treatment
Population: Participants 25 minutes after Naloxone or Placebo administration, among those who completed both intervention visits
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Cortisol | 3.22 nmol/L | Standard Deviation 2.18 |
| Placebo | Cortisol | 3.37 nmol/L | Standard Deviation 1.96 |
Secondary
Cortisol
Geometric Mean Salivary Cortisol level.
Time frame: 55 minutes post-treatment
Population: Participants 55 minutes after Naloxone or Placebo administration, among those who completed both intervention visits
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Cortisol | 3.61 nmol/L | Standard Deviation 2.26 |
| Placebo | Cortisol | 2.90 nmol/L | Standard Deviation 2.19 |
Comparison: 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.p-value: 0.06795% CI: [0.98, 1.61]t-test, 2 sided
Secondary
Subjective Opiate Withdrawal Scale
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Subjective Opiate Withdrawal Scale | 5.67 score on a scale | Standard Deviation 3.65 |
| Placebo | Subjective Opiate Withdrawal Scale | 5.03 score on a scale | Standard Deviation 3.58 |
Secondary
Subjective Opiate Withdrawal Scale (Abbreviated)
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Subjective Opiate Withdrawal Scale (Abbreviated) | 1.42 score on a scale | Standard Deviation 1.35 |
| Placebo | Subjective Opiate Withdrawal Scale (Abbreviated) | 1.53 score on a scale | Standard Deviation 1.5 |
Other Pre-specified
Impulsivity (Delayed Discounting)
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.
Population: All eligible participants randomized to either order of the intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Impulsivity (Delayed Discounting) | 0.69 Probability | Standard Deviation 0.21 |
| Placebo | Impulsivity (Delayed Discounting) | 0.57 Probability | Standard Deviation 0.29 |
Other Pre-specified
Reward-Driven Eating Scale (RED)
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
Population: All eligible participants who were randomized to either order of intervention conditions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Reward-Driven Eating Scale (RED) | 38.1 score on a scale | Standard Deviation 6.1 |
| Placebo | Reward-Driven Eating Scale (RED) | 36.8 score on a scale | Standard Deviation 5.2 |