Adjunctive Pregnenolone in Veterans With Mild TBI

NCT00623506 | Completed Results

• 1 other identifier: VA IRB# 01209
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Mild traumatic brain injury (TBI) is common among veterans who have served in OEF/OIF (Operation Enduring Freedom in Afghanistan/Operation Iraqi Freedom) and other theatres. Delayed symptoms may occur following TBI, including cognitive symptoms (impaired attention, processing speed, executive functioning), as well as behavioral symptoms such as anxiety, depression, and irritability (Fann et al. 2004; Holsinger et al. 2002). Neuroactive steroids have neuroprotective effects in rodent models of TBI (Djebaili et al. 2005; Djebaili et al. 2004; He et al. 2004; Pettus et al. 2005; Roof et al. 1997) and the neuroactive steroid pregnenolone and its sulfated derivative also markedly enhance learning and memory in rats (Akwa et al. 2001; Flood et al. 1992; Flood et al. 1995; Vallee et al. 1997; Vallee et al. 2003). In humans, reductions in pregnenolone (George et al. 1994) and its GABAergic metabolite allopregnanolone (Uzunova et al. 1998) have been associated with depressive symptoms. Pharmacological intervention with the neuroactive steroid pregnenolone could therefore result in a multi-targeted treatment approach, potentially improving cognitive deficits as well as anxiety and depression symptoms following TBI.

Conditions

Traumatic Brain Injury

Keywords

TBI; Pregnenolone; Cognition

Outcome Measures

Primary Outcomes (1)

• Brief Assessment of Cognition in Affective Disorders (BAC-A)

  Mean change scores (Week 2 minus Week 10) to assess cognitive changes. The BAC-A includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3. Mean change scores from week 2 and week 10 (Week 2 minus Week 10).

  Week 2, Week 10

Secondary Outcomes (2)

• Clinician Administered PTSD Scale (CAPS)

  Week 2, Week 10

• Quick Inventory of Depressive Symptomatology (QIDS)

  Week 2, Week 10

Study Arms (2)

1

ACTIVE COMPARATOR

Pregnenolone

Drug: Pregnenolone

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Pregnenolone DRUG

Placebo for two weeks (during placebo lead-in), then: Pregnenolone 100 mg in divided doses (50 mg, PO, BID) Pregnenolone 300 mg in divided doses (150 mg, PO, BID) Pregnenolone 500 mg in divided doses (250 mg, PO, BID)

1

Placebo DRUG

Placebo for two weeks (placebo lead in), then: Placebo equivalent to Pregnenolone arm: 100 mg in divided doses (50 mg, PO, BID) Placebo equivalent to Pregnenolone arm: 300 mg in divided doses (150 mg, PO, BID) Placebo equivalent to Pregnenolone arm: 500 mg in divided doses (250 mg, PO, BID)

2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age, any ethnic group, either sex
• History of mild TBI since September 2001. TBI occurring at age 18 or older.
• We will adhere to the operational definition of mild TBI suggested by the World Health Organization Task Force (Holm et al.2005), with the exception of the Glasgow Coma Scale Score criteria (not available for these participants).
• Ability to participate fully in the informed consent process.
• No anticipated need to alter medications for the 10-week duration of the study.

You may not qualify if:

• For this pilot study, we will exclude patients who report a history of seizures.
• Serious unstable medical illness. History of cerebrovascular accident, prostate, uterine, or breast cancer. Use of oral contraceptives or other hormonal supplementation such as estrogen.
• Current active suicidal and/or homicidal ideation, intent or plan.
• Current DSM-IV (Diagnostic and Statistical Manual, Fourth Edition) diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than TBI.
• Female patients who are pregnant or breast-feeding.
• Known allergy to study medication.

Sponsors & Collaborators

• Durham VA Medical Center: lead

Study Sites (1)

Durham VA Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Results Point of Contact

• Title: Christine E. Marx, MD
• Organization: Durham VA Medical Center

marx0001@mc.duke.edu

919 286-0411

Study Officials

• Christine E Marx, MD, MA

  Durham VAMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2008
• First Posted: February 26, 2008
• Study Start: January 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: November 1, 2012
• Last Updated: June 20, 2013
• Results First Posted: June 20, 2013

Record last verified: 2013-05

Locations

US (1)