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SchizophreniaPhase 2OligoTreatNCT06315972

Combining Clemastine and Aerobic Exercise to Treat Cognitive Dysfunction in Schizophrenia by Targeting Myelin Plasticity

A Phase 2 study testing clemastine (8 mg/day) in people with Schizophrenia, run by LMU Klinikum.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial summary

Schizophrenia (SZ) is a broad clinical entity characterized by different subjective symptoms,behavioural signs, and disease course. Research has pointed to numerous biological indicators tentatively associated with neurocognitive dysfunction, brain structural and neurochemical alterations. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Schizophrenia
What is being tested?
clemastine (8 mg/day)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
No sites listed yet
Study dates
Apr 2024to Apr 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • • Written informed consent obtained from the participant prior to performing any protocol-related procedures, including screening evaluations
  • A DSM-V diagnosis of schizophrenia or schizophrenia-spectrum disorder according to MINI interview
  • Age between 18 and 65 years EudraCT Number: 2022-000054-28 Confidential OligoTreat Study Protocol Version 2.0 06.09.2023 9 of 62
  • Total Positive and Negative Syndrome Scale (PANSS) score ≤ 75 at V0
  • Stable antipsychotic treatment dose for at least one week prior to inclusion
  • Stable CNS-active treatment substance and dose (e.g. antidepressants and mood stabilizers) for at least one week prior to inclusion
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  • Female participants with reproductive potential must have a negative beta- HCG serum pregnancy test as part of the screening visit
  • Female participants with reproductive potential must have a negative serum pregnancy test within seven days prior to randomization
  • Male participants and female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country at screening

Who cannot join

  • Patients who are unable to give informed consent
  • Coercive treatment at the time of study inclusion
  • Treatment-naïve schizophrenia defined as cumulative treatment with an antipsychotic agent lifetime for <30 days
  • Insufficient understanding of the German language
  • Patients with primary active (moderate or severe) substance use disorder (other than nicotine) according to MINI interview (DSM-V): patients fulfilling early (>3 months) or sustained (>12 months) remission criteria and/or with low severity of substance use disorder according to MINI are eligible for the study
  • Known clinically relevant CNS disorder(s), such as epilepsy or history of seizures
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  • Concomitant use of any other putative remyelinating therapy as determined by investigator
  • Co-occurrent unstable somatic condition
  • Known porphyria
  • Known narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy with urinary retention and bladder neck obstruction Current treatment with agents with strong anticholinergic properties, such as MAO-inhibitors, opioid antagonists, clozapine at the time of study inclusion
  • Known intolerance, allergy/contraindications to one of the study drugs or any of the excipients or other agents with similar chemical properties as the study drugs (such as other arylalkylamine antihistamines)
  • Clinically relevant liver and/or renal impairment (serum creatinine >1.5mg/dl or eGFR<30 ml/min/1.73 m2 at screening, AST or ALT > 2-times the upper limit of normal at screening)
  • Current treatment with macrolide-antibiotics (such as erythromycin, clarithromycine) or azole-type antimycotics
  • Clinically relevant cardiac comorbidities (i.e. Long QT-syndrome)
  • Current hypokalaemia and/or clinically relevant hyponatraemia at screening
  • Patient-reported hereditary galactose-intolerance and/or Lapp lactosedeficiency, lactose intolerance and/or glucose-galactose malabsorption
  • Pregnancy or breast-feeding
  • Concurrent enrolment in another clinical trial where the participant is receiving an IMP or participation in another clinical trial with IMP during the last 30 days before inclusion or 7 half-lives of previously used IMP, whichever is longer.
  • For the optional MRI assessments: potential MRI contraindication(s)

About this study

Schizophrenia (SZ) is a broad clinical entity characterized by different subjective symptoms,behavioural signs, and disease course. Research has pointed to numerous biological indicators tentatively associated with neurocognitive dysfunction, brain structural and neurochemical alterations. Cognitive deficits occur as early as the prodromal phase of the illness and significantly determine its outcome. Pathophysiologically, SZ is regarded as a disconnectome disorder in which frontal and temporal brain regions are functionally disconnected, which contributes substantially to the development of cognitive dysfunction.

Impaired connectivity is related to synaptic (microconnectivity) and myelin (macroconnectivity) plasticity. With design-based stereology, a decreased number of oligodendrocytes (OLs) in the CA4 hippocampal subregion as the basis for disturbed myelination and impaired cognition, but also a decrease in the prefrontal cortex were observed. Animal studies demonstrated that clemastine enhances remyelination by increasing the differentiation of oligodendrocyte precursor cells (OPCs) and showed that aerobic exercise increases the rate of remyelination and proliferation of OPCs; this clinically meaningful effect of aerobic exercise is stronger in combination with clemastine. Furthermore, aerobic exercise improves everyday functioning, measured by the Global Assessment of Functioning (GAF) scale, and cognitive dysfunction in SZ and increases hippocampal volume, especially the volume in the hippocampal CA4 subregion. This regional volume change correlates negatively with global and cell-specific polygenic risk scores (PRSs), indicating that OPCs are involved in the genetic risk mechanisms and disturbed plasticity underlying SZ. In patients with multiple sclerosis, 90 days' administration of clemastine fumarate 10.72 mg/day, corresponding to clemastine 8 mg/day, significantly decreased the P100 latency delay of visual evoked potentials (VEPs) as a sign of myelin repair. In a bicentric, randomized, double-blind, controlled phase IIb clinical trial with a 2-arm parallel group design in patients with SZ, the study will compare the effects of aerobic exercise training plus clemastine vs. aerobic exercise training plus placebo over a period of 3 months on 1) everyday functioning and 2) working memory as primary outcomes.

Conditions
Schizophrenia
Being tested
clemastine (8 mg/day), Placebo
Medical subject headings
Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • clemastine (8 mg/day)Drug

    add-on clemastine (8 mg/day) + aerobic exercise training

  • PlaceboDrug

    add-on placebo + aerobic exercise training

Study groups in NCT06315972
Study groupRoleWhat they receive
Experimental interventionExperimentalApplication of double-blind add-on clemastine at a dosage of 8 mg/day (morning: 4 mg; evening: 4 mg) + aerobic exercise training 50 min 3x/week over a period of 3 months
Receives: Drug: clemastine (8 mg/day)
Control interventionPlacebo comparatorApplication of double-blind add-on placebo (morning and evening) + aerobic exercise training 50 min 3x/week
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. change in Global Assessment of Functioning

    change in Global Assessment of Functioning (GAF) scores from the start of the intervention period (V1.1) to primary outcome visit after 90-93 days of treatment (V2).

    Measured: 3 months

  2. change in working memory performance

    change in working memory performance assessed by the n-back test (2-back level, d-prime) from V1.1 to V2.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2024
  2. Study startApr 2024 (estimated)
  3. Primary completionNov 2026 (estimated)
  4. Study completionApr 2028 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06315972
Sponsor's protocol ID
2022-000054-28
Acronym
OligoTreat
Status last verified
Mar 2024
First submitted
12 Mar 2024
Last updated
20 Mar 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing clemastine (8 mg/day) in people with Schizophrenia, run by LMU Klinikum.

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 9 inclusion and 19 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: opening soon, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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 Global Assessment of Functioning (time frame: 3 months). 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?

On the ClinicalTrials.gov record for NCT06315972.

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 20 Mar 2024.

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