Memory Enhancement by Gamma-hydroxybutyrate vs. Trazodone in Major Depressive Disorder.

30 healthy adults and 30 patients with major depressive disorder, will take part in three single-application pharmacological interventions (GHB vs. Trazodone vs. placebo p.o.) to test potential effects of these drugs on nocturnal memory consolidation. All participants will be assessed with mood state questionnaires, tests of emotional, procedural and declarative memory consolidation, polysomnography, EEG and neuroinflammatory biomarkers. At experimental nights, learning tasks are performed prior to sleep. The next morning, recalling tasks are performed. Each subject will pass through 5 study nights (1 screening, 1 adaptation and 3 experimental nights).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: GHB; Drug: Trazodone; Drug: Placebos

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • ZH
    • Zürich, ZH, Switzerland, 8032
      • Psychiatric University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Arm 1 (healthy controls):

• Healthy participants,
• Non-smoker,
• Age 20-65 years

Arm 2 (patients with depression):

• Diagnosis of major depression (DSM-V),
• Selective Serotonin-Reuptake-Inhibitor (SSRI) or Selective Serotonin-Noradrenalin-Reuptake-Inhibitor (SSNRI) medication,
• Age 20-65 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: healthy controls	Drug: GHB; 50 mg/kg GHB at one experimental night; Drug: Trazodone; 1.5 mg/kg trazodone at one experimental night; Drug: Placebos; placebo oral solution (placebo for GHB) and placebo pills (placebo for trazodon)
Experimental: Major Depressive Disorder	Drug: GHB; 50 mg/kg GHB at one experimental night; Drug: Trazodone; 1.5 mg/kg trazodone at one experimental night; Drug: Placebos; placebo oral solution (placebo for GHB) and placebo pills (placebo for trazodon)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
slow wave sleep amount	slow wave sleep time (minutes) during the experimental night	1 night
performance in emotional memory consolidation tasks by Emotional Picture Memory Task (EPMT)	results in EPMT are measured as number of recognized pictures (1-150)	10 hours after encoding
performance in procedural memory consolidation tasks by Finger Sequence-Tapping Task (FSTT)	results in FSTT are measured as number of correct sequences typed in 30seconds	10 hours after encoding
performance in declarative memory consolidation tasks by Paired Word List Task (PAWL)	Results in PAWL are expressed as number of correct word pairs recalled (1-40).	10 hours after encoding
Blood levels of Brain Derived Neurotrophic Factor (BDNF).	Assessed in serum samples collected by venipuncture using a butterfly needle. Unit of measure as blood concentration (ng/l or mg/ml)	9 hours after solid drug administration
homeostatic sleep pressure by Psychomotor Vigilance Task	Results are measured in number of correct answers	10 hours after solid drug administration
homeostatic sleep pressure by N-back Task	Results are measured in number of correct answers	10 hours after solid drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep quality assessed by Morgen Questionionnaire (MQ)	structured interview about sleep quality on the previous night. Subjektive sleep time will be assessed in minutes (0-480 minutes). Long sleep time will be a good outcome. Interview time of 5minutes.	at 8:00 a.m. after experimental night 1,2 and 3
Sleep quality assessed by Karolinska Schläfrigkeitsskala (SKK)	Subjects will report their subjective sleep pressure in a 1-10 points scale. Low values mean low sleep pressure and better therapy response.	at 8:00 a.m. after experimental night 1,2 and 3
Cortisol Saliva Response (CAR)	Cortisol concetration in Saliva (nmol/l)	0minutes, 15minutes, 30minutes, 45minutes and 60minutes after awekening
Score on Positive and Negative Affect Schedule (PANAS)	self-report questionnaire that consists of two 10-item scales to measure both positive and negative affect. Each item is rated on a 5-point scale of 1 (not at all) to 5 (very much)	8 hours after solid drug administration

Collaborators and Investigators

• Sponsor: Erich Seifritz

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Actual): April 6, 2022
• Study Completion (Actual): April 6, 2022

Study Registration Dates

• First Submitted: August 28, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Trazodone
• Other Study ID Numbers: Mem-GHB-TRA-Study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No