Trial Outcomes & Findings for Estrogen and Serotonin on Changing Brain Chemistry (NCT NCT01208324)
NCT ID: NCT01208324
Last Updated: 2021-04-02
Results Overview
To replicate and extend our previous behavioral findings of an interaction between estrogen therapy (ET) and tryptophan depletion on verbal memory in a group of early menopausal women randomized to receive ET. Blood-oxygen-level dependent or BOLD signal is the outcome of BOLD imaging, which is a technique used in functional MRI. BOLD signal reflects changes in regional cerebral blood flow which delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change means that between scans the BOLD signal i.e. blood flow in that region has increased, a negative percent change means that the BOLD signal has decreased between scans.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
47 participants
Primary outcome timeframe
8 weeks
Results posted on
2021-04-02
Participant Flow
2 participants included in the Placebo Patch/ Active then Sham group completed Test Day 1, but did not receive a patch. 1 participant included in the Placebo Patch/ Sham then Active group completed Test Day 1, but did not receive a patch.
Participant milestones
| Measure |
Active Patch: Active Tryptophan, Then Sham Tryptophan
Participants assigned to receive the Active ET patch, and sequence of active tryptophan followed by sham tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Active Patch: Sham Tryptophan, Then Active Tryptophan
Participants assigned to receive the Active ET patch, and sequence of sham tryptophan followed by active tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Sham Patch: Active Tryptophan, Then Sham Tryptophan
Participants assigned to receive the Sham patch, and sequence of active tryptophan followed by sham tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Sham Patch: Sham Tryptophan, Then Active Tryptophan
Participants assigned to receive the Sham ET patch, and sequence of sham tryptophan followed by active tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
|---|---|---|---|---|
|
Pre-randomization of Patch
STARTED
|
14
|
15
|
10
|
8
|
|
Pre-randomization of Patch
Test Day 1
|
14
|
15
|
10
|
8
|
|
Pre-randomization of Patch
Test Day 2
|
14
|
15
|
8
|
5
|
|
Pre-randomization of Patch
COMPLETED
|
14
|
15
|
8
|
5
|
|
Pre-randomization of Patch
NOT COMPLETED
|
0
|
0
|
2
|
3
|
|
Post-randomization of Patch
STARTED
|
14
|
15
|
8
|
5
|
|
Post-randomization of Patch
Test Day 3
|
13
|
15
|
8
|
5
|
|
Post-randomization of Patch
Test Day 4
|
13
|
15
|
8
|
5
|
|
Post-randomization of Patch
COMPLETED
|
13
|
15
|
8
|
5
|
|
Post-randomization of Patch
NOT COMPLETED
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Active Patch: Active Tryptophan, Then Sham Tryptophan
Participants assigned to receive the Active ET patch, and sequence of active tryptophan followed by sham tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Active Patch: Sham Tryptophan, Then Active Tryptophan
Participants assigned to receive the Active ET patch, and sequence of sham tryptophan followed by active tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Sham Patch: Active Tryptophan, Then Sham Tryptophan
Participants assigned to receive the Sham patch, and sequence of active tryptophan followed by sham tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Sham Patch: Sham Tryptophan, Then Active Tryptophan
Participants assigned to receive the Sham ET patch, and sequence of sham tryptophan followed by active tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
|---|---|---|---|---|
|
Post-randomization of Patch
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Estrogen and Serotonin on Changing Brain Chemistry
Baseline characteristics by cohort
| Measure |
Active Patch: Active Tryptophan, Then Sham Tryptophan
n=13 Participants
Participants assigned to receive the Active ET patch, and sequence of active tryptophan followed by sham tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Active Patch: Sham Tryptophan, Then Active Tryptophan
n=15 Participants
Participants assigned to receive the Active ET patch, and sequence of sham tryptophan followed by active tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Sham Patch: Active Tryptophan, Then Sham Tryptophan
n=8 Participants
Participants assigned to receive the Sham patch, and sequence of active tryptophan followed by sham tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Sham Patch: Sham Tryptophan, Then Active Tryptophan
n=5 Participants
Participants assigned to receive the Sham ET patch, and sequence of sham tryptophan followed by active tryptophan. There will be four successful\* TRP depletion test sequences: two test sequences one week apart prior to randomization to ET or PT, and two sequences one week apart following approximately 6-weeks of double-blind ET or PT. Each TRP depletion test day will involve ingestion of 70 capsules. During one of each pair of tests, the 70 capsules will contain 31.5 g of lactose (sham depletion; for participants who are not lactose intolerant) or 31.5 g of microcellulose (sham depletion; for participants who have mild to moderate lactose intolerance), while during the other test they will contain a total of 31.5 g of amino acids, but no tryptophan.
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
55.15 years
n=5 Participants
|
55.69 years
n=7 Participants
|
54.94 years
n=5 Participants
|
54.16 years
n=4 Participants
|
55.18 years
n=21 Participants
|
|
Sex/Gender, Customized
Women
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
41 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
32 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Adverse Childhood Experiences (ACE) Questionaire
High ACE
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Adverse Childhood Experiences (ACE) Questionaire
Low ACE
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 8 weeksTo replicate and extend our previous behavioral findings of an interaction between estrogen therapy (ET) and tryptophan depletion on verbal memory in a group of early menopausal women randomized to receive ET. Blood-oxygen-level dependent or BOLD signal is the outcome of BOLD imaging, which is a technique used in functional MRI. BOLD signal reflects changes in regional cerebral blood flow which delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change means that between scans the BOLD signal i.e. blood flow in that region has increased, a negative percent change means that the BOLD signal has decreased between scans.
Outcome measures
| Measure |
High Ace
n=16 Participants
Participants with an adverse childhood experience (ACE) score greater than or equal to 2.
|
Low Ace
n=24 Participants
Participants with an adverse childhood experience (ACE) score less than 2.
|
|---|---|---|
|
Percent Change in BOLD Signal
|
-.43 percentage of BOLD signal changes
Interval -0.65 to -0.22
|
.20 percentage of BOLD signal changes
Interval -0.16 to 0.21
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: This outcome measure was not assessed. No participants were analyzed and no data was collected.
To evaluate the extent to which effects of ET (estrogen therapy) and TRP-D on verbal working memory are mediated through the dorsolateral prefrontal cortex.
Outcome measures
Outcome data not reported
Adverse Events
Active Patch: Active Tryptophan, Then Sham Tryptophan
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Active Patch: Sham Tryptophan, Then Active Tryptophan
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Sham Patch: Active Tryptophan, Then Sham Tryptophan
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Sham Patch: Sham Tryptophan, Then Active Tryptophan
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place