Mild-Intensity Whole Body Hyperthermia (WBH) for Major Depressive Disorder

NCT03787290 | Suspended Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 2020P002424
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Overall, the objective of this pilot study is to utilize the IL-6 receptor antagonist tocilizumab to prospectively evaluate the role of IL-6 in the antidepressant and immunological effects of whole body hyperthermia (WBH). The study seeks to replicate findings thus far that WBH has an antidepressant effect by administering the intervention at a site not involved in studies to date. Moreover, the current proposal may help the investigators better understand the role of IL-6 in the pathogenesis and treatment of depression which might point to novel immune-based interventions for Major Depressive Disorder (MDD). Finally, the current proposal holds promise for better understanding of a novel treatment for MDD, which is among the leading causes of health-related disability in the world.

Conditions

Major Depressive Disorder

Keywords

hyperthermia; whole-body hyperthermia; depression; major depressive disorder; cytokine; inflammation; immunological; mechanism of action; tocilizumab

Outcome Measures

Primary Outcomes (1)

• Inventory of Depressive Symptomatology Self-Report (IDS-SR)

  The IDS-SR is a self-administered questionnaire assessing depressive severity. 30 questions focus on depressive symptoms experienced over the past 7 days. Each question is scored from 0-3, for a total minimum score of 0 and a total maximum score of 84 (appetite and weight items are split into two questions each, one for increase and one decrease, but counted once only, so there are effectively 28 items). Higher scores indicate more severe depression. Ranges correspond to depressive severity as follows: 0-13 = no or minimal depression; 14-25 = mild depression; 26-38 = moderate depression; 39-48 = severe depression; 49-84 = very severe depression. A decrease of 50% or more in the score is considered to be a response to treatment, while a final score of 11 or less is considered remission. Primary study outcomes will be between-group differences (tocilizumab vs. placebo) in total IDS-SR score change from Week 0 (Visit 2) to Week 1 (visit 3).

  Week 0 (Visit 2) to Week 1 (visit 3) [approximately 7 days]

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Participants will receive tocilizumab followed by whole-body hyperthermia

Drug: Tocilizumab; Device: Whole-Body Hyperthermia

Placebo

ACTIVE COMPARATOR

Participants will receive a placebo followed by whole-body hyperthermia

Drug: Placebo; Device: Whole-Body Hyperthermia

Interventions

Tocilizumab DRUG

participants will receive a single subcutaneous injection of tocilizumab (162 mg)

Tocilizumab

Placebo DRUG

participants will receive a single subcutaneous injection of saline

Also known as: Saline

Placebo

Whole-Body Hyperthermia DEVICE

subjects' core temperature will be increased to 38.5 degrees Celsius (typically 60-120 minutes) then they will begin a 60-minute cool-down phase

Also known as: Heckel HT3000

Placebo; Tocilizumab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent for study participation.
• Males and females between the age of 18 and 65 years.
• Have a current primary psychiatric diagnosis of major depressive disorder (MDD) of at least 4 weeks duration, as defined by DSM-5 criteria using the MINI v.7.0.
• A Screening and Baseline visit Clinician-Administered Inventory of Depressive Symptomatology Questionnaire (IDS-C30) score ≥ 25.
• Screening visit high-sensitivity C-reactive protein (CRP) concentration ≤ 5 mg/L (based on evidence that cytokine antagonism has an independent antidepressant effect in depressed patients with elevated CRP above this cut-off).

You may not qualify if:

• Any of the following medical conditions:
• cardiovascular disease (other than controlled hypertension)
• seizure disorder, history of cerebrovascular accident (CVA) or other serious neurological condition (e.g., Parkinson's disease, multiple sclerosis, seizure disorder \[except childhood febrile seizures\], dementia or delirium)
• presence or history of neoplasia (other than resected non-melanotic skin cancer)
• endocrinopathies (diabetes mellitus types I and II, Cushing's disease, Addison's disease)
• active autoimmune disease (e.g., rheumatoid arthritis, Hashimoto's thyroiditis, inflammatory bowel disease)
• chronic infection (e.g., hepatitis B or C or human immunodeficiency virus \[HIV\] infection)
• acute kidney injury or Chronic Kidney Disease
• any history of or current diagnosis of thrombosis or thrombophilia; if it is unclear whether a subject has received this diagnosis, a signed release will be obtained to contact the subject's treating physician and obtain accurate diagnostic information. Depending on the recommendation of the treating physician, the subject may undergo appropriate testing with the treating physician to verify the diagnosis, and if the tests produce negative findings, the subject may be allowed to enter the study.
• any history of recurrent or recurring HSV (Herpes simplex)
• any active enclosed infection (e.g., dental abscess, joint infection)
• hemophilia or other cause for excessive bleeding (e.g., platelet disorder)
• fever (Temp \> 99) of unknown origin at the time of screen
• laboratory evidence of undiagnosed hypothyroidism or any change in treatment for hypothyroidism in the 3 months prior to screening.
• significant electrocardiogram abnormalities

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• heckel medizintechnik GmbH: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02139, United States

Location

Related Publications (3)

• Janssen CW, Lowry CA, Mehl MR, Allen JJ, Kelly KL, Gartner DE, Medrano A, Begay TK, Rentscher K, White JJ, Fridman A, Roberts LJ, Robbins ML, Hanusch KU, Cole SP, Raison CL. Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Aug 1;73(8):789-95. doi: 10.1001/jamapsychiatry.2016.1031.

  PMID: 27172277 BACKGROUND

• Hanusch KU, Janssen CH, Billheimer D, Jenkins I, Spurgeon E, Lowry CA, Raison CL. Whole-body hyperthermia for the treatment of major depression: associations with thermoregulatory cooling. Am J Psychiatry. 2013 Jul;170(7):802-4. doi: 10.1176/appi.ajp.2013.12111395. No abstract available.

  PMID: 23820835 BACKGROUND

• Hale MW, Lukkes JL, Dady KF, Kelly KJ, Paul ED, Smith DG, Raison CL, Lowry CA. Whole-body hyperthermia and a subthreshold dose of citalopram act synergistically to induce antidepressant-like behavioral responses in adolescent rats. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):162-168. doi: 10.1016/j.pnpbp.2017.06.006. Epub 2017 Jun 12.

  PMID: 28619470 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Hyperthermia; Depression; Inflammation

Interventions

tocilizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries; Behavioral Symptoms; Behavior; Pathologic Processes

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The randomization list maintained by the Research Pharmacy will contain the treatment assignment, along with a letter code (A or B) corresponding to the two treatment groups. During the study period and continuing until the major hypotheses have been tested and reported, the correspondence of letter-coded treatment assignment to actual treatment (tocilizumab or placebo) will be known only by pharmacy staff. The study principal investigator (PI), study coordinators, clinicians conducting outcome assessments, and study statistician, as well as research assistants interacting with patients or entering study data and laboratory technicians performing/reporting biomarker assays, will have no access to any subject's treatment assignment. Only after the study statistician has completed and reported analyses by coded treatment assignment for the study aims articulated in this protocol will the correspondence between letter codes and actual treatment be revealed to study personnel.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomization will be conducted by randomly permuted blocks of 4. The randomization schedule will be created by a statistician who has no other role in the study data collection or analysis. The randomization schedule will be sent directly from the statistician to the Research Pharmacy which will maintain the list. Qualifying study subjects will be assigned the next sequential treatment assignment on the randomization schedule, in the order they are randomized. Participants will be randomized on a 1-to-1 allocation to one of two study arms: 1) tocilizumab followed by whole body hyperthermia (WBH); or 2) placebo followed by whole body hyperthermia (WBH). At the time of randomization, the study coordinator will contact the Research Pharmacy to complete the coded treatment assignment described below.

Study Record Dates

• First Submitted: October 27, 2018
• First Posted: December 26, 2018
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: November 13, 2025

Record last verified: 2025-11

Locations

US (1)