Major Depressive DisorderNCT01478113
Stimulant Enhancement of Well-Being Therapy for Depression
A study testing Amphetamine/dextroamphetamine and Well-being therapy in people with Major Depressive Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study aims to identify a novel enhancement strategy for residual symptoms of major depressive disorder (MDD) Dopamine (DA) has been viewed as a "pleasure neurotransmitter" for over 30 years. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Amphetamine/dextroamphetamine and Well-being therapy
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to Jul 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Outpatients between 18 and 60 years of age.
- Experiencing residual symptoms after 8 weeks of SSRI therapy, with at least 4 weeks at a stable dose of the current agent prior to randomization.
- Fulfillment of DSM-IV diagnostic criteria for MDD during the present episode of illness with continuing residual symptoms.
- A score of 14 to 26 on the 31-item Hamilton Depression Rating Scale (HAM-D-31) at screening and randomization.
- A Clinical Global Impression of Severity (CGI-S) score of 3 or 4 at screening and randomization.
Who cannot join
- Treatment within 4 weeks of randomization with any non-SSRI antidepressant, antipsychotic, mood stabilizer, standing benzodiazepine, stimulant, or stimulant-like agent.
- Allowed exception 1: Concomitant benzodiazepines, at a stable dose, that have been taken for at least one year with no history of abuse.
- Allowed exception 2: Effexor, duloxetine (Cymbalta) or milnacipran (Savella) can serve as main SSRI treatment.
- Allowed exception 3: Combinations of SSRIs (ex. Zoloft \& Lexapro concomitantly) are acceptable as main SSRI treatment.
- If a subject endorses "yes" or "agree" of any item from 12 to 23 on the CHRT, it would indicate active suicidality and would be exclusionary.
- Significant suicide risk.
Show all 18Show fewer
- Current treatment-resistant episode of MDD.
- A primary diagnosis of an Axis I disorder other than MDD.
- History of a psychotic disorder, dysthymia, antisocial personality disorder, BPD, or mental retardation.
- History of a substance use disorder, with the exception of nicotine dependence, within 12 months prior to screening.
- History of stimulant abuse, prescription drug abuse, and eating disorders.
- Initial insomnia at screening that is not adequately controlled by medications. Subjects with recent history of unstable insomnia as defined by active or poorly controlled symptoms of insomnia within the past 1 month will be excluded.
- Co-morbid medical conditions including a structural heart defect or rhythm abnormality that might be exacerbated by stimulant therapy; hypertension as measured by a resting sitting systolic blood pressure of > 149mmHg or diastolic blood pressure > 95mmHg; tachycardia as measured by a sitting pulse rate of >100 bpm or <50 bpm after resting for 5 minutes.
- Allergy, hypersensitivity, intolerance, or history of non-responsivity to stimulant medications.
- History of non-responsivity to CBT or well-being therapy.
- Women who are pregnant or breastfeeding.
- Glaucoma or hyperthyroidism
- Current concomitant therapy is only permitted if it is supportive therapy (not specifically CBT) and has been ongoing for at least one year. However, if a subject has been in therapy for less than one year and wishes to discontinue or take a hiatus from their current therapy before coming in for a screening visit, this will be allowed. Additionally, subjects may not enter into other talk therapies for the duration of this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Depression Clinical and Research Program
Boston, Massachusetts, 02114
About this study
This study aims to identify a novel enhancement strategy for residual symptoms of major depressive disorder (MDD) Dopamine (DA) has been viewed as a "pleasure neurotransmitter" for over 30 years. Yet recent data from animal and human studies suggest that dopamine has greater effects on "wanting" than on "liking." Therefore, the investigators of this study have hypothesized that amphetamine/d-amphetamine (AMPH), a medication which increases dopamine transmission in the reward centers of the brain, may have a more powerful antidepressant effect in combination with well-being therapy (WBT), a specific type of cognitive-behavioral therapy, which helps individuals with depression to increase their contact with natural rewards and decrease reward-interfering thoughts.
The investigators will test their hypothesis by randomizing 40 individuals with residual symptoms of depression, already taking an antidepressant that affects serotonin (e.g. Prozac, Paxil), to 8 weeks of treatment with either WBT in combination with AMPH, or WBT with pill placebo. The effectiveness of each treatment will be measured using a reliable scale, called the Hamilton Depression Rating Scale.
The investigators have also hypothesized that people assigned to the stimulant/WBT group will have greater improvements in functioning, well-being, and positive affectivity than those the people assigned to the WBT/placebo group.
Read the detailed description
The study will have 11 visits occur over 8 weeks with study visits scheduled weekly or biweekly.
Detailed Description:
The study visit occurrences are as follows:
- Week 0- Screening Visit
- Week 1- Baseline Visit
- Week 2- one phone visit and one clinic visit in one week
- Week 3- one phone visit and one clinic visit in one week
- Week 4- one visit in one week
- Week 5- one visit in one week
- Week 6- one visit in one week
- Week 7- one visit in one week
- Week 8- one visit in one week
WBT description Four licensed therapists, who have been trained and certified in WBT, will provide weekly sessions of 30 to 50 minutes in duration. Therapists will follow the procedures outlined in the WBT manual. The initial sessions (weeks 0-2) will be focused on identifying and contextualizing episodes of well-being. The intermediate sessions (weeks 3-5) will be focused on modifying cognitions and behaviors, which lead to premature interruption of well-being, and optimizing cognitions and behaviors, which have been idiographically linked to enhanced well-being. Final sessions (weeks 6-8) will apply the Psychological Well-Being scales (PWB) to refine treatment according to Ryff's dimensions of well-being. Additional principles and techniques of WBT include reappraisal, mood-charting, scheduling of activities, shaping, problem-solving, and assertiveness training.
Medication Schedule Participants will receive treatment with the stimulant, amphetamine/d-amphetamine, or matched placebo.
Participants will start at 1 pill (placebo or 5 mg amphetamine/d-amphetamine) in the morning and 1 pill (placebo or 5 mg amphetamine/d-amphetamine) at noon. The treatment will then be flexibly adjusted up or down by a study clinician based on participant's response. Dose ranges will be 1-3 pills (placebo or 5 mg amphetamine) in the morning and 1-3 pills (placebo or 5 mg amphetamine) at noon.
- Conditions
- Major Depressive Disorder
- Being tested
- Amphetamine/dextroamphetamine, Placebo, Well-being therapy
- Keywords
- Major Depressive Disorder, Therapy, Medication study, Depression, Therapy study
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amphetamine/dextroamphetamineDrug
Also called Adderall, Adderall XR
The amphetamine/dextroamphetamine will be in a pill formulation. The dosage of the amphetamine/dextroamphetamine will be flexibly adjusted up or down by a study clinician based on the participant's response. Dose ranges will be 1-3 pills (placebo or 5 mg amphetamine) in the morning and 1-3 pills (placebo or 5 mg amphetamine) at noon.
PlaceboDrug
Also called Sugar-pill
The placebo will match the dextroamphetamine in form, dosage, frequency, and duration.
Well-being therapyBehavioural
Also called WBT
Therapy sessions will last between 30-50 minutes. The sessions will take place at every visit after the screening visit.
| Study group | Role | What they receive |
|---|---|---|
| WBT + amphetamine/dextroamphetamine | Active comparator | In the active group, participants will receive treatment with Well-being therapy and amphetamine-dextroamphetamine. Receives: Drug: Amphetamine/dextroamphetamine; Behavioral: Well-being therapy |
| WBT + placebo | Placebo comparator | In the placebo group, participants will receive treatment with Well-being therapy and pill placebo. Receives: Drug: Placebo; Behavioral: Well-being therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hamilton-Depression Rating Scale(SIGH-D)-17 Items
Comparison between the 2 groups of the percentage of subjects in remission, as defined by a HAM-D-17 score of < 8 at endpoint visit 11/week 8 of treatment, or early termination visit.
Measured: Baseline and visit 11/week 8 of treatment, or between baseline and early termination visit.
Change in Hamilton-Depression Rating Scale(SIGH-D)-31 Item
Comparison between the 2 groups of the percentage of participants who have responded to the treatment (response is defined here as a 50% or greater improvement on the HAM-D-31 score) between Baseline and Visit 11 or Early Termination Visit.
Measured: Baseline to Visit 11 (which is week 8 of treatment) or Early Termination Visit.
Secondary outcomes (5)
Change in Psychological Well-being Scale (PWB)
Well-being improvement: Comparison between the 2 groups of changes on the PWB at Baseline and Visit 11/Early Termination.
Measured: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in the Snaith-Hamilton Pleasure Scale (SHAPS)
Improvement of anhedonia: Comparison between the 2 groups of changes on the SHAPS at Baseline and Visit 11/Early Termination.
Measured: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in Behavioral Inhibition/Activation Scale (BIS/BAS)
Improvement of deficits in behavioral activation: Comparison between the 2 groups of changes on the BIS/BAS at Baseline and Visit 11/Early Termination.
Measured: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in Positive and Negative Affective Scale (PANAS)
Improvement of deficits in positive affectivity: Comparison between the 2 groups of changes on the PANAS at Baseline and Visit 11/Early Termination.
Measured: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in Functioning on Short Form-12(SF-12)
Functional improvement: Comparison between the 2 groups of changes on the SF-12 scale at Baseline and Visit 11/Early termination visit.
Measured: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startFeb 2012
- Primary completionJul 2014
- Study completionJul 2015
Why it stopped: PI left the institution and was no funding to continue study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Harvard Medical School (HMS and HSDM)
- Responsible party
- Principal investigator, Maren Nyer, Massachusetts General Hospital
- Investigators
- Maurizio Fava, MD, Principal investigator, Massachusetts General Hospital and Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01478113
- Sponsor's protocol ID
- 2011P002148
- Other IDs
- 2011D002171
- Status last verified
- Mar 2017
- First submitted
- 26 Sep 2011
- Last updated
- 26 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: No plan to make IPD available.
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stimulant Enhancement of Well-Being Therapy for Depression
- ClinicalTrials.gov ID
- NCT01478113
- Acronym / sponsor ID
- 2011P002148
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, Therapy, Medication study, Depression, Therapy study
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left the institution and was no funding to continue study.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Harvard Medical School (HMS and HSDM)
- Study start
- Feb 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 23 Nov 2011 (estimated)
- Results
- Posted 26 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to identify a novel enhancement strategy for residual symptoms of major depressive disorder (MDD) Dopamine (DA) has been viewed as a "pleasure neurotransmitter" for over 30 years. Yet recent data from animal and human studies suggest that dopamine has greater effects on "wanting" than on "liking." Therefore, the investigators of this study have hypothesized that amphetamine/d-amphetamine (AMPH), a medication which increases dopamine transmission in the reward centers of the brain, may have a more powerful antidepressant effect in combination with well-being therapy (WBT), a specific type of cognitive-behavioral therapy, which helps individuals with depression to increase their contact with natural rewards and decrease reward-interfering thoughts.
The investigators will test their hypothesis by randomizing 40 individuals with residual symptoms of depression, already taking an antidepressant that affects serotonin (e.g. Prozac, Paxil), to 8 weeks of treatment with either WBT in combination with AMPH, or WBT with pill placebo. The effectiveness of each treatment will be measured using a reliable scale, called the Hamilton Depression Rating Scale.
The investigators have also hypothesized that people assigned to the stimulant/WBT group will have greater improvements in functioning, well-being, and positive affectivity than those the people assigned to the WBT/placebo group.
Detailed description
The study will have 11 visits occur over 8 weeks with study visits scheduled weekly or biweekly.
Detailed Description:
The study visit occurrences are as follows:
- Week 0- Screening Visit
- Week 1- Baseline Visit
- Week 2- one phone visit and one clinic visit in one week
- Week 3- one phone visit and one clinic visit in one week
- Week 4- one visit in one week
- Week 5- one visit in one week
- Week 6- one visit in one week
- Week 7- one visit in one week
- Week 8- one visit in one week
WBT description Four licensed therapists, who have been trained and certified in WBT, will provide weekly sessions of 30 to 50 minutes in duration. Therapists will follow the procedures outlined in the WBT manual. The initial sessions (weeks 0-2) will be focused on identifying and contextualizing episodes of well-being. The intermediate sessions (weeks 3-5) will be focused on modifying cognitions and behaviors, which lead to premature interruption of well-being, and optimizing cognitions and behaviors, which have been idiographically linked to enhanced well-being. Final sessions (weeks 6-8) will apply the Psychological Well-Being scales (PWB) to refine treatment according to Ryff's dimensions of well-being. Additional principles and techniques of WBT include reappraisal, mood-charting, scheduling of activities, shaping, problem-solving, and assertiveness training.
Medication Schedule Participants will receive treatment with the stimulant, amphetamine/d-amphetamine, or matched placebo.
Participants will start at 1 pill (placebo or 5 mg amphetamine/d-amphetamine) in the morning and 1 pill (placebo or 5 mg amphetamine/d-amphetamine) at noon. The treatment will then be flexibly adjusted up or down by a study clinician based on participant's response. Dose ranges will be 1-3 pills (placebo or 5 mg amphetamine) in the morning and 1-3 pills (placebo or 5 mg amphetamine) at noon.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| WBT + amphetamine/dextroamphetamine | Active comparator | Drug: Amphetamine/dextroamphetamine, Behavioral: Well-being therapyIn the active group, participants will receive treatment with Well-being therapy and amphetamine-dextroamphetamine. |
| WBT + placebo | Placebo comparator | Drug: Placebo, Behavioral: Well-being therapyIn the placebo group, participants will receive treatment with Well-being therapy and pill placebo. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Outpatients between 18 and 60 years of age.
- Experiencing residual symptoms after 8 weeks of SSRI therapy, with at least 4 weeks at a stable dose of the current agent prior to randomization.
- Fulfillment of DSM-IV diagnostic criteria for MDD during the present episode of illness with continuing residual symptoms.
- A score of 14 to 26 on the 31-item Hamilton Depression Rating Scale (HAM-D-31) at screening and randomization.
- A Clinical Global Impression of Severity (CGI-S) score of 3 or 4 at screening and randomization.
Key exclusion criteria (18 listed)
- Treatment within 4 weeks of randomization with any non-SSRI antidepressant, antipsychotic, mood stabilizer, standing benzodiazepine, stimulant, or stimulant-like agent.
- If a subject endorses "yes" or "agree" of any item from 12 to 23 on the CHRT, it would indicate active suicidality and would be exclusionary.
- Significant suicide risk.
- Current treatment-resistant episode of MDD.
- A primary diagnosis of an Axis I disorder other than MDD.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amphetamine/dextroamphetamineAlso: Adderall, Adderall XRThe amphetamine/dextroamphetamine will be in a pill formulation. The dosage of the amphetamine/dextroamphetamine will be flexibly adjusted up or down by a study clinician based on the participant's response. Dose ranges will be 1-3 pills (placebo or 5 mg amphetamine) in the morning and 1-3 pills (placebo or 5 mg amphetamine) at noon. | Drug | WBT + amphetamine/dextroamphetamine |
| PlaceboAlso: Sugar-pillThe placebo will match the dextroamphetamine in form, dosage, frequency, and duration. | Drug | WBT + placebo |
| Well-being therapyAlso: WBTTherapy sessions will last between 30-50 minutes. The sessions will take place at every visit after the screening visit. | Behavioural | WBT + amphetamine/dextroamphetamine, WBT + placebo |
Primary outcome
Change in Hamilton-Depression Rating Scale(SIGH-D)-17 Items
Time frame: Baseline and visit 11/week 8 of treatment, or between baseline and early termination visit.
Comparison between the 2 groups of the percentage of subjects in remission, as defined by a HAM-D-17 score of < 8 at endpoint visit 11/week 8 of treatment, or early termination visit.
Change in Hamilton-Depression Rating Scale(SIGH-D)-31 Item
Time frame: Baseline to Visit 11 (which is week 8 of treatment) or Early Termination Visit.
Comparison between the 2 groups of the percentage of participants who have responded to the treatment (response is defined here as a 50% or greater improvement on the HAM-D-31 score) between Baseline and Visit 11 or Early Termination Visit.
5 secondary outcomes
Change in Psychological Well-being Scale (PWB)
Time frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in the Snaith-Hamilton Pleasure Scale (SHAPS)
Time frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in Behavioral Inhibition/Activation Scale (BIS/BAS)
Time frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in Positive and Negative Affective Scale (PANAS)
Time frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Change in Functioning on Short Form-12(SF-12)
Time frame: Baseline to Visit 11 (which is 8 weeks of treatment) or Early Termination Visit.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No plan to make IPD available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maurizio Fava, MD principal investigator
Massachusetts General Hospital and Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Amphetamine/dextroamphetamine and Well-being therapy in people with Major Depressive Disorder, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hamilton-Depression Rating Scale(SIGH-D)-17 Items (time frame: Baseline and visit 11/week 8 of treatment, or between baseline and early termination visit.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2017.